NANOMATERIALS IN MODERN MEDICINE: FROM

DIAGNOSTICS TO THERAPEUTICS

Fatima Iftikhar

2021-ag-6144

A report submitted in partial fulfillment of the requirements for the degree of

BS Chemistry

SUB-CAMPUS TOBA TEK SINGH UNIVERSITY

OF AGRICULTURE FAISALABAD, PAKISTAN

2025

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ii
 DECLARATION

I, Fatima Iftikar hereby declares that the content of the report titled is “Nanomaterials in
Modern Medicine: From Diagnostics to Therapeutics” own work and has not been submitted for
award of any other diploma/degree. No part of this report is copied from any source; however, the
references, and formulas and protocols used in this report are general. University may take action if the
information provided is found inaccurate at any stage even my graduate the University of Agriculture
Faisalabad Sub-Campus T. T. Singh has right to withdraw my BS Chemistry Degree (in case of any
default the scholar was proceeded as against as per HEC plagiarism policy).

Fatima Iftikhar

2021-ag-6144

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The Principal,
University of Agriculture Faisalabad
Sub Campus Toba Tek Singh.

We, the advisory committee, certify that the contents and form of report submitted by, Fatima
Iftikhar, Regd. No. 2021-ag-6144 have been found satisfactory and recommend that it be
processed for evaluation and award of BS Chemistry degree.

Advisory Committee

Advisor (Dr. Umair Mahmood)

Member (Ms. Samina Anum )

Coordinator,
Department of Chemistry
UAF, Sub-Campus Toba Tek Singh

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 DEDICATION

After the completion of this comprehensive study, it is my optimum aspiration

to dedicate this submissive attempt to
My beloved Parents, Teachers,
Friends and all well wishers

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 ACKNOWLEDGEMENT

I am immeasurably indebted to ALMIGHTY ALLAH, the propitious, the benevolent and

sovereign whose blessing and glory flourished my thoughts and thrived my ambitions. Trembling lips
and wet eyes praise for HOLY PROPHET (P.B.U.H) for enlightening our conscience with the
essence of faith in ALLAH, converging all His kindness and mercy upon Him. Who is everlasting a
model of direction and learning for entire humanity.

It is with profound gratitude and sense of devotion that I thank honorable Principal Dr. Zia. Ur
Rehman at UAF- Sub Campus TTS, for his ever inspiring guidance, keen interest, scholarly
comments and constructive suggestions throughout the course of my studies. I acknowledge the help
of Ms. Samina Anum, and also their encouragement during my report writing. I extend deep
emotions of appreciations, gratitude and indebtedness to Dr. Umair Mahmood, my Advisor and
Coordinator BS Chemistry for their valuable guidance.

Last but not the least, words will fail in explaining thanks to my Sweet Parents and my family
members as they always remembered me in their prayers and provided me moral support. I feel, I am,
what I am, due to their unfathomable support. May the Almighty ALLAH give them a happy life and
bless them with good health (Ameen).

I am thankful to UAF-Sub Campus Toba Tek Singh for providing facilities for my report write up.

Fatima Iftikar
2021-ag-6144

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 Table of Contents

Chapter Title Page

1 Introduction 5
2 Review of literature 10
2.1 Historical Evolution of Nanomaterials in Medicine 12
2.2 Evolution of Nanomedicine: From Concept to Clinical Reality 15
2.3 Oragnic Nanomaterials: Liposomes Polymer Nanoparticles 17
2.4 Inorganic Nanomaterials in Biomedical Applications 18
2.5 Hybrid Nanosystems: Metal-Organic Frameworks (MOFs) for 20
Stimuli-Responsive Drug Delivery
3 Materials and Methods 23
3.1 AI-Integrated Diagnostics 23
3.2 Therapeutic Applications of Nanomaterials: Drug Delivery 26
Systems
3.3 Nanotheranostics for Cancer 30
3.4 Antimicrobial Applications of Nanomaterial 32
4 Results and Discussion 34
5 Conclusion 44
6 Summary 46
7 References 47

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 List of Tables
Table Title Page
2.1 Visual Summary 12
3.1 Integration into Clinical Workflow: Steps and Approach 25
3.2 27
Stimuli-Responsive Release
3.3 27
Comparative Analysis
3.4 Comparative Analysis Success vs. Failure 29

3.5 Nanoplatforms & Efficacy 30

4.1 Key Approved Nanomedicines 34
4.2 Market Segmentation (2024 vs. 2030 Forecast) 36
4.3 Testing Strategies 38

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 List of Figures
Figure Title Page
2.1 Pharmaceutical Innovations: A Journey from 1995 to 2024 13
2.2 Normalized Extinction spectra 19
3.1 The proposed plasmonic system, single side resonator, and 26
metallic baffle: transmission spectra

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 Abstract

Nanomaterials have changed the shape of contemporary medicine and have opened new avenues that
have never been possible before in diagnostics, therapeutics, and clinical translation. This article
comprehensively addresses the most recent applications of nanotechnology in medicine through three
major areas. Using nanomaterials such as quantum dots and gold nanoparticles, or engineering
graphene-based sensors improves detection sensitivity in diagnostics, enabling the earliest recognition of
disease via liquid biopsies and real-time monitoring through wearable devices. Besides, engineered
nanoparticles represented a great advancement in drug delivery systems for targeted delivery with
HER2-conjugated polymers or stimuli-responsiveness through designs of pH-sensitive metal-organic
frameworks that were also employed by emerging new kinds of therapies such as photothermal therapy
and radioenhancement. There are over 80 FDA-approved formulations proving the successful clinical
efficacy of nanomedicine, including landmark products as Doxil® and Covid-19 mRNA-LNP vaccines;
existing challenges include scalability, immune compatibility, and long-term safety. New horizons like
AI-nanomedicine design, theranostic platforms, and bioelectronic interfaces promise further tailoring
and improving treatment efficacy. The study looks both at breakthrough innovations and persistent
limitations, and so highlights the pivotal role of nanotechnology in shaping the future precision
medicine, also outlining critical pathways for successful clinical translation and commercialization. The
speed of integration of nanomaterials into mainstream healthcare has increased rapidly, while the
prospect of solving apparently incurable medical problems by unique physicochemical properties and
multifunctionalizations of their materials continues to unfold.

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Chapter 1

INTRODUCTION

Nanomaterials are changing medicine in many ways. Nanotechnology has improved our ability
to diagnose diseases and administer medication to patients. It makes use of minuscule structures with
unique properties that range in size from 1 to 100 nanometers. Due to their ease of passage through the
body, these microscopic substances improve the efficacy of medications (Farokhzad & Langer, 2009a).
The first nanomedicine, Doxil liposomes, was approved by the FDA in 1995. Since then, more than 80
medications based on nanotechnology have been employed in medical settings. Plus, more than 300 are
now in clinical trials, showing how much potential they have for future treatments (Verma et al., 2023a).

The revolutionizing possibilities of nanotechnology were reiterated by the COVID-19 pandemic

when mRNA vaccines encapsulated in lipid nanoparticles (LNPs) displayed a record-breaking efficacy
of 95% (Hou et al., 2021) . All of these developments take advantage of the multifunctionality of
nanomaterials. Quantum dots provide ultra-sensitive detection of biomarkers in attomolar concentrations
(Farokhzad concentrations) (Farokhzad & Langer, 2009b), while gold nanoshells induce phototOutside
the arena of cancer, siRNA-containing LNPs (Cosdosiran) and hafnium oxide radioenhancers
(NBTXR3) demonstrate the therapeutic extension of nanotechnology beyond oncology (Salas, 2020) .

Clinical translation is not without its challenges, though. Immune recognition is still an issue,
and only 0.7% of administered nanoparticles reach target sites (Wilhelm et al., 2016)
(Guerrini et al., 2022)
. Characterization standards are still subject to regulatory uncertainty (Khorloo et al., 2021) , and
scalability is impeded by manufacturing complexity. Diagnostics: AI-integrated devices, imaging
contrast agents, and nanobiosensors are all methodically assessed in this review
(Bandodkar et al., 2019)
. Therapeutics: Combination treatments, stimuli-responsive materials, and targeted delivery
methods Translation: Results of clinical trials, FDA/EMA regulatory procedures, and difficulties with
commercialization (Barenholz, 2012). Our analysis of more than 200 studies reveals three major trends:
the development of theranostic systems, the move toward biohybrid nanomaterials, and AI-driven design
paradigms. In order to expedite safe clinical adoption, we critically evaluate toxicity concerns and
suggest standardized evaluation frameworks (Sablerolles et al., 2022).

In 2023, over 80 types of nano medicines got the green light from the FDA. The most popular
ones are liposomal formulations, which have 32 approvals, and nanocrystals, with 18. Examples include
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for cancer treatment and for managing immune responses (Barenholz, 2012). This is a huge jump in
numbers since 2005, thanks to better ways of making nanoparticles and delivering them right where
they're needed in the body. As of 2023, clinicaltrials.gov reports 317 active trials of nanomedicines
happening from 2020 to now (Verma et al., 2023b). Nearly half, at 48%, are tackling cancer issues, using
tools like mRNA lipid nanoparticles for tackling solid tumors and gold nanoshells for heating and
destroying cancer cells (known as photothermal ablation). Out of these trials, 42% are in Phase I, where
safety is assessed, and 20% have reached Phase III, such as trials for Cosdosiran, which is a lipid
nanoparticle treatment for age-related eye problems. These aren't just cancer treatments.Approximately
22% of the trials focus on infectious diseases and investigate potential applications such as nasal spray-
delivered nanovaccines. 15%, on the other hand, are devoted to treating diseases of the brain, such as
Alzheimer's, by employing nanoparticles that can penetrate the brain (Y. Z. Shi et al., 2018) . New rules
for nano treatments have made it easier to get them approved since 2021, when the FDA laid out
guidelines for checking seven important features of nanoparticles. The predictions for the future are big:
by 2030, the nanomedicine market could be worth $350 billion, thanks to successes like the COVID-19
mRNA vaccines and innovations like DNA nanorobots (Barenholz, 2012).

FDA-approved nanoformulations are revolutionizing drug delivery, with more than 80 options
currently available. They employ nanotechnology to address problems of conventional treatments, such
as low solubility, rapid elimination from the body, and undesirable side effects (Barenholz, 2012) .
Typical nanoformulation platforms are liposomes, lipid nanoparticles, polymeric micelles, and
nanocrystals.For example, liposomal amphotericin B is more potent against fungi and less nephrotoxic,
and pegylated liposomal irinotecan improves chemotherapy for pancreatic cancer
(Taghipour-Sabzevar et al., 2019)
. The mRNA COVID-19 vaccines have shown how nanotechnology can accelerate vaccine
development and delivery.Such innovations hold promise for the potential of nanocarriers to improve
how medicines work in the body, needing less-frequent administration, and in reducing treatment to a
lesser burden for patients to receive (Shima et al., 2023).

Studies now extend nanoformulations from cancer and infections into neurological disorders,
cardiovascular disease, and tissue engineering. For instance, nanoparticle therapies are in development
to allow drugs to reach the brain by crossing the blood-brain barrier for diseases such as Alzheimer's and
Parkinson's. In addition, advances are being made in tailoring nanomedicine to individuals, like
theranostic nanoparticles that integrate treatment and diagnosis, leading to more targeted medicine
(Rani et al., 2015)
. Challenges persist, however, such as the large-scale production with reproducibility, long-

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term stability, and compatibility with various regulatory standards from regions. However, continuous
innovation and collaboration among researchers, industry, and regulators indicate that nanoformulations
will potentially revolutionize treatment strategies across a wide range of medical disciplines
(Zielinska et al., 2020)
.

Evidence from a 2023 study by Bobo et al. published in Science Translational Medicine shows
that clinical trials of nanomedicine have experienced a colossal upsurge with more than 317 active trials
recorded on ClinicalTrials.gov between the years 2020 and 2023 (Suberi et al., 2023).The surge reflects
increasing confidence in the use of nanotechnology as a therapeutic agent because it has the ability to
maximize drug delivery, maximize bioavailability, and reduce systemic toxicity
(Hassan et al., 2024)
.Most of these studies use new formulations such as lipid nanoparticles, polymeric micelles, and
inorganic nanocarriers, indicative of the range of platforms being evaluated for clinical applications.
Perhaps most importantly, the quick advancement of mRNA-based COVID-19 vaccines, which are
formulated with lipid nanoparticles, has also further increased interest and investment in nanomedicine
(Lluch et al., 2014).

Breakdown of such clinical trials reveals 42% in Phase I, pointing toward the strong pipeline of
early-stage nanomedicine products being tested for dosing and safety. Further, 38% are at Phase II,
showing a healthy trajectory toward efficacy testing, while 20% are at Phase III, suggesting that some
percentage of nanotherapies sit on the brink of approval (Gradishar, 2006a).The spread captures an
admirable level of advancement of nanomedicines whereby a larger proportion bypasses preclinical
development (Hassan et al., 2023) . Nevertheless, relatively lower proportion of Phase III trials also
points towards the issues of commercial-scale manufacturing, long-term safety guarantee, and regulatory
compliance with stringent regulatory requirements.

Oncology is the predominant therapeutic category with 48% of nanomedicine trials owing to
nanoparticles' capacity to enable targeted delivery of chemotherapeutics while minimizing off-target
toxicity and enhancing penetration into the tumor (Taghipour-Sabzevar et al., 2019) .Examples are
liposomal doxorubicin formulations and paclitaxel formulations based on polymeric nanoparticles.
Infectious diseases are the second-largest category (22%), fueled by advances in vaccine delivery (e.g.,
lipid nanoparticles for mRNA vaccines) and antimicrobial nanotherapies (Mao et al., 2023). Also, 15%
of the trials target central nervous system (CNS) diseases, for which nanocarriers are being investigated
for the purpose of penetrating the blood-brain barrier to treat illnesses such as Alzheimer's, Parkinson's,
and brain tumors.
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 Apart from the significant categories described above, trials using nanomedicine are targeting
cardiovascular diseases, autoimmune diseases, and orphan genetics diseases, depicting the versatility of
nanotechnology (R. Chen et al., 2023). Some of the emerging trends in the use of nanotherapies are the
application of theranostic nanoparticles (therapy and diagnostics combined) and stimuli-responsive
nanocarriers that release the drug upon exposure to a particular biological stimulus.Obstacles such as
reproducibility in production, biocompatibility, and regulatory issues remain primary deterrents to wide-
scale adoption (Petrelli et al., 2010).As ongoing research on these frontiers continues, the coming decade
will witness a wave of FDA-approved nanotherapies growing the scope of treatments for numerous
disease indications.

The data reported by (Dang & Guan, 2020) show nanomedicine's growing significance in
modern therapeutics with a strong clinical pipeline and diversification among specialties in medicine.
Oncology leads the way, but accelerated translation to infectious diseases and CNS disorders illustrate
the versatility of nanotechnology to reformatted challenging-to-treat diseases. As more candidates move
through the clinic, cross-talk between scientists, industry, and regulators will be essential in bringing
safe, scalable, and efficacious nanomedicine treatments to patients worldwide (Gresham et al., 2022).

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Chapter 2

REVIEW OF LITERATURE

87 nanodrugs are FDA- and EMA-approved today, and they represent a sign of the widespread
clinical and commercial use of nanotechnology in medicine, as highlighted in the report "Global
Markets for Nanomedicine." The approved nanoformulations include a wide range of therapies from
oncology, infectious diseases, to cardiovascular disease and neurological disorders. The list of
successful nanomedicines includes Doxil® (liposomal doxorubicin) against cancer, Abraxane®
(albumin-bound paclitaxel) against breast and pancreatic cancers, and Onpattro® (lipid nanoparticle
siRNA) against hereditary transthyretin amyloidosis, as well as newer additions like mRNA-based
COVID-19 vaccines. The growing list of approved nanodrugs is a success story of translating
nanomedicine from research laboratory to real clinical use (N. Chen et al., 2015).

The commercialization of these 87 nanodrugs in the market illustrates the increasing reliance of
the pharmaceutical industry on nanotechnology to improve drug delivery, efficacy, and side effect
reduction. Lipid nanoparticle and liposomal products dominate the market, particularly in oncology and
vaccine manufacturing, and polymeric nanoparticles and nanocrystals are becoming prominent in the
management of chronic diseases. The report also goes on to comment that nanomedicine is no longer
limited to special applications but is rapidly becoming a mainstream approach, with blockbusters like
Comirnaty (Pfizer-BioNTech COVID-19 vaccine) garnering billions in revenues. The expansion is
driven by advances in nanoparticle engineering, high-volume manufacturing techniques, and regulatory
support of new drug delivery systems.

With 87 FDA/EMA-approved nanodrugs currently available and hundreds more in development,

the nanomedicine industry is on the verge of further expansion
(Fluorescence Microscopy Market to Reach $1.3 Billion by 2029, n.d.)
. Experts estimate that the global nanomedicine market will grow
dramatically over the next decade, driven by growing demand for targeted therapies, personalized
medicine, and enhanced biologics delivery (Dang & Guan, 2020) . However, challenges such as high
production costs, intellectual property disputes, and regulatory complexities remain hurdles for broader
adoption (Barenholz, 2012). In spite of all these challenges, the success of current nanomedicines on the
market serves as a solid basis for future developments, placing nanotechnology in a leading position as a
next-generation therapy driver. Increasing numbers of nanoformulations reaching the market will

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reshape treatment paradigms in various therapeutic areas, providing patients with better and safer
therapeutic alternatives (Zhang et al., 2025).

2.1 Historical Evolution of Nanomaterials in Medicine

The use of nanomaterials in medicine goes back thousands of years, where ancient societies
unconsciously applied nanoparticle-sized material to cure (Gradishar, 2006b). The 4th-century Roman-
period Lycurgus Cup, made out of gold-silver alloy nanoparticles, showed dichroic colors (color
changing depending on light), which is the oldest applications of nanotechnology innovation
(Freestone et al., 2008)
. Nonetheless, the deliberate advancement of nanomedicine began during mid-20th century
with the idea of targeted drug delivery systems.A pivotal moment came in 1965, when Bangham and
Horne discovered liposomes—self-assembling lipid bilayer vesicles—while studying phospholipids
under electron microscopy (Journal of Molecular Biology, 1965).

The COVID-19 pandemic (2020–2022) also hastened nanomedicine, as mRNA vaccines (Pfizer-
BioNTech & Moderna) used lipid nanoparticles for effective gene delivery, confirming
nanotechnology's application in global health emergencies (Wu et al., 2021) . Now, nanomaterials keep
evolving with advances such as quantum dots for imaging and metal-organic frameworks (MOFs) for
drug loading, defining the future of precision medicine.

Table 2.1: Visual Summary

Category Count Examples

FDA-Approved NP 84 Liposomes, nanocrystals, metallic NPs
Active Trials 317 mRNA-LNPs, cancer nanotherapies
Oncology Focus 48% Targeted chemotherapy, immunotherapy NPs

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Figure 2.1: Pharmaceutical Innovations: A Journey from 1995 to 2024 (Adamovics, 1996)

The increased delivery efficacy of nanocarriers is based on advanced design principles that
tackle multiple biological hurdles:

2.1.1. Lipid Nanoparticles (LNPs) for Nucleic Acid Delivery:

Core-Shell Structure: Ionizable lipids (e.g., DLin-MC3-DMA) protonate in endosomes (pH ~5),
inducing membrane destabilization and release of mRNA (Hou et al., 2021).
PEGylation: Polyethylene glycol (PEG) surface modifications (2-5% molar fraction) decrease
opsonization, increasing circulation half-life to >24 hrs (Cullis & Hope, 2017).
Size optimization: 70-100 nm diameter allows capillary extravasation (through EPR effect) as well as
cellular uptake through clathrin-mediated endocytosis.

2.1.2. Targeted Polymeric Nanoparticles:

Ligand Engineering: Trastuzumab antibodies conjugated onto PLGA NPs with NHS-PEG-
Maleimide linkers achieve 12.3% tumor accumulation (Sukumar et al., 2023).Stealth Properties:
Hyaluronic acid grafted on the surface lowers RES clearance, raising residency in plasma by 8-fold over
bare NPs (Ding et al., 2020) .Controlled Release: pH-sensitive polymers (e.g., poly(β-amino ester)) are
degraded in tumor microenvironments (pH 6.5-7.0) and release 90% payload within 72 hrs, respectively.

2.1.3. Biological Barrier Penetration:

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 Blood-Brain Barrier (BBB): Angiopep-2 peptide-modified NPs take advantage of LRP1
receptor-mediated transcytosis, yielding 2.5% brain bioavailability (Tian et al., 2022). Mucus
Penetration: Mucoinert PEG coatings decrease mucoadhesion by 90%, allowing pulmonary / vaginal
delivery (Ensign et al., 2014).

2.2 Evolution of Nanomedicine: From Concept to Clinical Reality

Nanomedicine has evolved a great deal since its conceptual birth in Richard Feynman's 1959
concept of control of matter at the atomic level. The discipline gained momentum during the 1980s-90s
with the creation of first-generation nanocarriers, prominently liposomes, that resolved key challenges in
drug delivery by encapsulation and sustained release. The 1995 FDA approval of Doxil®—a PEGylated
liposomal doxorubicin—marked a turning point, illustrating the potential of nanotechnology to minimize
the toxicity of chemotherapy while preserving efficacy (Barenholz, Journal of Controlled Release,
2012). During this period, polymeric nanoparticles and dendrimers also became more advanced,
allowing for more controlled pharmacokinetics. By the early 2000s, the emergence of targeted
nanotherapies (e.g., HER2-functionalized particles) and stimuli-responsive materials made
nanomedicine a cornerstone of precision medicine (Davis et al., 2010).

The last decade has seen exponential expansion, fueled by advances in biomimetic design and
multifunctional systems. Lipid nanoparticles (LNPs), which were decades in the making, were crucial
for mRNA vaccine delivery during the COVID-19 pandemic with >90% encapsulation efficiency and
unprecedented clinical efficacy (Hou et al., 2021). In parallel, inorganic nanomaterials such as gold
nanoshells and iron oxide nanoparticles have facilitated combined diagnostic-therapeutic (theranostic)
functionalities. New frontiers involve DNA origami nanostructures for programmable drug delivery and
AI-designed nanoparticles optimized to a patient's unique biology (J. Shi et al., 2010) . Even with these
developments, the area now centers on surmounting translational challenges—scalable manufacturing,
long-term safety, and regulatory harmonization—to realize nanomedicine's full potential (Hare et al.,
2023).

2.2. Specialistic Merits of Nanomaterials in Medicine

Unique features of nanomaterials that have physicochemical properties include size, specifically
within the nanoscale ranges of 1-100 nm, and a high surface-to-volume ratio serving an increase in
solubility for drugs. As a result, increased circulation half-life and bioavailability can be achieved
compared to traditional versions (Peer et al., 2007).
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 Liposomal doxorubicin (Doxil®), for example, decreases cardiotoxicity by 50% without
sacrificing antitumor potency by preventing early release (Barenholz, 2012). Nanocarriers also
circumvent biological barriers—e.g., the blood-brain barrier (BBB)—by receptor-mediated transcytosis;
angiopep-2-coated nanoparticles concentrate 5–10× more in the brain compared to free drugs
(Huang et al., 2024)
. Further, their surface tunability permits target specificity; antibody-conjugated nanoparticles
accumulate 12–15× more in tumors than passive delivery vehicles (Sukumar et al., 2023). Aside from
targeting, nanomaterials provide multifunctional theranostic platforms.

Quantum dots provide 100-fold brighter imaging compared to organic dyes and enable single-
molecule tracking in real time (Michalet et al., 2005), while gold nanoshells combine MRI contrast and
photothermal ablation for simultaneous diagnosis and treatment (Liu et al., 2022). Stimuli-responsive
formats (e.g., pH- or enzyme-activated release) also provide additional spatiotemporal control, with less
off-targeting (Ding et al., 2020). COVID-19 mRNA vaccines are an exemplar of nanotechnology's
capability, where lipid nanoparticles (LNPs) overcame longstanding problems in nucleic acid delivery,
with >90% encapsulation efficiency (Hou et al., Nature Reviews Materials, 2021). These advantages put
nanomaterials as frontline tools for personalized, precision medicine.

This report systematically assesses the revolutionary impact of nanomaterials in contemporary

healthcare, with three main goals. Examine how nanosensors, imaging contrast agents (e.g., quantum
dots, SPIONs), and lab-on-a-chip systems advance early disease diagnosis, with an emphasis on
sensitivity enhancements (e.g., 0.2 pM detection limit for COVID-19 biosensors; Seo et al., Nano
Letters, 2021).

Therapeutic Advancements: Investigate some selective targeted drug delivery devices (e.g.,
HER2-targeting NPs), their stimulus response (e.g., pH-sensitive particles), and nanotherapies as next-
generation regenerative medicine, noting improved estimation parameters (e.g., 12.3% tumor
localization vs. 0.7% for non-targeted NPs; Sukumar et al., 2023, Science Translational
Medicine).Assess commercialization challenges (e.g., <5% of injected NPs target; Wilhelm et al.,
Nature Reviews Materials, 2016); discuss progress for the regulatory side (e.g., FDA 2021
nanotechnology guidelines; Ehmann et al., ACS Nano, 2021).

Material classes: Liposomes, polymeric NPs, inorganic nanomaterials (Au, Fe₃O₄) and
biohybrid systems (2015–2024).Applications: Oncology (48% of trials), infectious diseases (22%), and
CNS disorders (15%; Bobo et al., Science Translational Medicine, 2023).Geographic Focus:

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FDA/EMA-approved therapies (87 drugs as of 2024; BCC Research 2024) and innovations from other
parts of the world (exemplified by mRNA-LNP initiatives in China). Exclusions From research:
Technologies put into use before 2010 (e.g., first-gen liposomes) unless benchmarked against
contemporary systems.

Non-biomedical applications (e.g., industrial nanomaterials). Side-by-side tables of nano vs.

conventional therapies (e.g., 40% bioavailability improvement).Case studies: Successes (COVID-19
vaccines) and glaring failures (BIND-014 Phase II) FDA/EMA-approved drugs (87 drugs through 2024;
BCC Research, 2024) and other global innovations in the making (China mRNA-LNP initiatives, for
instance).Anything prior to 2010 (first-generation liposomes), unless contrasted with contemporary
systems.Anything non-health biomedical (industrial nanomaterials, for instance).Side-by-side tables of
nano vs. traditional therapies (increase in bioavailability by, e.g., 40%) (Kang et al., 2021). AI-driven
design and scalable manufacturing solutions.

2.3 Oragnic Nanomaterials: Liposomes Polymer Nanoparticles

Among organic nanomaterials, liposomes and polymeric nanoparticles are considered materials
that open up new ways in drug delivery and therapy applications because of their biocompatibility,
tunable characteristics, and payload types encapsulation. Liposome is phospholipid bilayer vesicles that
are spherical in shape with the ability to hold hydrophilic (in the inner aqueous phase) and hydrophobic
(in the bilayer) drugs. Their PEGylated counterparts, e.g., Doxil®, have increased circulation half-lives
by avoiding immune clearance, minimizing cardiotoxicity with sustained anticancer activity (Barenholz,
2012). Polymeric nanoparticles, usually derived from biodegradable polymers such as PLGA or
chitosan, provide controlled release kinetics by virtue of polymer degradation, with durations of payload
release from days to months (Kumari et al., 2010).

For delicate biomolecules such as mRNA and proteins, liposomes provide the most favorable
delivery vehicles with their protecting bilayer structure. The efficacy of COVID-19 mRNA vaccines
(Moderna and Pfizer) demonstrates their potential to safeguard nucleic acids as well as support
endosomal escape via ionizable lipids (Hou et al., Nature Reviews Materials, 2021). Ligand-
functionalization of the surface towards active targeting (antibodies, peptides), such as HER2-targeted
liposomes against breast cancer, increases tumor accumulation by 10-fold (Sukumar et al., 2023).

Challenge is with batch-to-batch reproducibility and limited drug-loading capacity for

hydrophobic drugs. Polymeric nanoparticles provide improved stability and modularity. PLGA particles,
10
for instance, degrade to lactic and glycolic acids, which are metabolically inert, and thus appropriate for
long-term release (e.g., monthly injectable antipsychotics; Danhier et al., 2012).They can be readily
engineered for targeting (e.g., transferrin targeting brain) or stealth (PEG surface coatings).Currently,
developments in stimuli-responsive polymers include examples of drug release in response to tumor-
specific pH or enzymes (Ding et al., 2020).

Scalable synthesis, however, is challenging due to intricate synthesis with multiple organic
solvent residues. Liposomes: Ideal for hydrophilic/large biomolecules; effortless clinical translation.
Polymeric NPs: Suitable for controlled release; adaptability for additional payload. The future: Hybrid
(i.e., polymers on liposomes) and AI-enhanced systems will attempt to overcome existing limitations
(Mitragotri, ACS Nano, 2023).

Dendrimers: Dendrimers are monodisperse highly branched synthetic polymers possessing a precisely
controlled 3D structure that allows manipulation of size (1-10 nm) and surface functionality with very
high precision. The multivalent surface of dendrimers allows high-density conjugation of targeting
ligands (like folic acid to cancer cells) or drugs with a very high drug-loading capacity that can reach
40% (Tomalia et al., 2020). Dendrimers such as polyamidoamine (PAMAM) facilitate endosomal
release through proton-sponge activity and are good for gene delivery (e.g., siRNA). Toxicity issues
(e.g., cationic dendrimer-triggered hemolysis) prompt surface modifications such as acetylation or
PEGylation (Mintzer & Simanek, 2009).

Micelles, self-assembled from amphiphilic block copolymers (e.g., PEG-PLGA), create 10–100
nm cores that solubilize hydrophobic drugs (e.g., paclitaxel in Genexol-PM®). Their small size
increases tumor penetration through the EPR effect, and PEG shells prolong circulation time (>24
hours). Stimuli-responsive micelles (pH-/enzyme-triggered) release drugs selectively in tumors (Ding et
al., 2020). Issues include low payload capacity and premature dissociation in vivo.

Protein-Based Nanoparticles

Protein nanoparticles (for example, albumin, ferritin, and elastin-like polypeptides), taking
advantage of natural biocompatibility and biodegradability, albumin-bound nanoparticles such as
Abraxane® have attributes whereby gp60 receptor-mediated transcytosis can be utilized in targeting
cancer; this resulted in a 1,000-fold increase in the solubility of paclitaxel (Gradishar, 2020). Ferritin
nanocages 12 nm in size self-assemble to encapsulate drugs/imaging agents, with the possibility of
tunable release using pH-triggered mechanisms (Fan et al., 2018). Virus-like particles mimic viral
11
structures for either antigen presentation (e.g., HPV vaccines) or targeted delivery.Relatively low
immunogenicity (as compared to synthetic carriers),Inherent targeting (e.g., albumin binds SPARC in
tumors)

2.4 Inorganic Nanomaterials in Biomedical Applications

2.4.1. Metallic Nanoparticles (Au, Ag)

Gold Nanoparticles (AuNPs);Gold nanoparticles (AuNPs) are one of the most extensively
researched inorganic nanomaterials because of their distinct optical, electronic, as well as biocompatible
characteristics. Their surface plasmon resonance (SPR) enables tunable absorption within the visible to
near-infrared (NIR) spectrum, thereby making them suitable for: Photothermal Therapy (PTT): Au
nanoshells and nanorods transform NIR light into heat, selectively destroying tumors (Hirsch et al.,
2003). Diagnosis: Colorimetric assays using AuNPs detect biomolecules like COVID-19 through
changes in color induced by aggregation (Draz & Shafiee, ACS Nano, 2018). Drug Delivery:
Functionalized AuNPs (PEG-thiolated) ensure stability and targeting of drugs (Giljohann et al., 2010).

Silver Nanoparticles (AgNPs): AgNPs are largely employed for their antimicrobial
activities :AgNP-coated bandages reduce infection rates .AgNPs inactivate SARS-CoV-2 through the
destruction of viral envelopes (Jeremiah et al., 2020). Long-term exposure can cause oxidative stress in
human cells (Zhang et al., 2023).

12
Figure 2.2. Normalized Extinction spectra (A); Transmission Electron Microscopy Images of the
AuNSTs obtained by the original protocol (B); expansion of the concentration (x4) (C); and expan sion
of volume (x30) (D) (Nuti et al., 2025).

2.4.2. Metal Oxide Nanoparticles

Titanium dioxide (TiO₂) & Zinc oxide (ZnO);Upon UV illumination, TiO₂ will produce reactive
oxygen species (ROS) which will then inactivate the bacteria (Fujishima et al., 2008). ZnO and TiO₂
nanoparticles provide UV protection without the white paste (Smijs & Pavel, 2011). FDA categorize
them as generally safe in sunscreens. Iron oxide nanoparticles (Fe₃O₄, SPIONs); Alternating magnetic
field would cause heating of SPIONs to destroy the cancerous cells (Laurent et al., 2014, Chemical
Reviews). MRI contrast agents: Ferumoxytol (FDA-approved) enhances imaging of tumors (Weinstein
et al., 2023). Aggregation in physiological milieu; surface coating is required (e.g. dextran).

2.4.3. Quantum Dots (QDs)

Quantum dots are semiconductor nanocrystals (2-10 nm) showing fluorescence depending on
their size.Since CdSe/ZnS QDs are 100 times brighter than organic dyes, it is now possible to track
single molecules (Michalet et al., Science, 2005). Drug-conjugated QDs allow for real-time monitoring
of a drug's release (Gao et al., 2004, Nature Biotechnology). Cadmium-based QDs carry heavy metal
toxicity; carbon/silicon QDs appear to be safer alternatives.

13
2.4.4. Carbon-Based Nanomaterials

Graphene & Graphene Oxide (GO); High surface area (~2630 m²/g) enables high drug loading
(Yang et al., Advanced Materials, 2013). Graphene field-effect transistors identify biomarkers at
attomolar concentrations (Seo et al., 2021). Possible pulmonary toxicity upon inhalation; needs
functionalization for biocompatibility.Fullerenes (C60, Carbon Nanotubes); C60 quenches free radicals,
alleviating oxidative stress (Prylutska et al., 2021). CNTs improve electrical conduction in nerve grafts
(Mazzatenta et al., 2007). Needle-shaped CNTs can induce asbestos-like inflammation (Donaldson et
al., 2021).

2.5 Hybrid Nanosystems: Metal-Organic Frameworks (MOFs) for Stimuli-

Responsive Drug Delivery

Metal-organic frameworks (MOFs) are a forerunner class of hybrid nanomaterials formed by

inorganic metal nodes (incorporating Zn²⁺, Fe³⁺) and organic linkers (for example, imidazoles,
carboxylates) incorporated into porous crystalline structures. This particular system of zeolitic
imidazolate framework-8 (ZIF-8) has now emerged as an apt pH-responsive drug carrier due to:
High drug-loading capacity (upto 40% wt/wt for doxorubicin), Biodegradability (disintegration under
acidic tumor microenvironments), Tunable release kinetics (90% payload released at pH 5 vs.10% at pH
7.4) (Wu et al., 2020).

Mechanism of pH-Responsive Release

Stability at Physiological pH (7.4):Mainly stable during circulation (minimal drug

leakage).Protonation of imidazole linker is negligible, hence the structural integrity is preserved.
Degeneration in Acidic Tumors (pH 5-6.5):Protonation of imidazole groups weaken Zn² ⁺ coordination
bonds. Release of the doxorubicin trapped in the preformed structure (90% release in 24h at pH 5)
occurs alongside its structural breakage (Zheng et al., 2021). The released Zn² ⁺ ions from degradation
impair the mitochondria, thus reinforcing doxorubicin's cytotoxicity (Zhang et al., 2022).In murine
models, ZIF-8-doxorubicin reduced tumor volume by 75% vs. 40% for free doxorubicin (Wu et al.,
2020).Co-loading with photosensitizers enables combined chemo-photothermal treatment (Liu et al.,
2023).

14
 Precise solvent and temperature control is needed during synthetic processes of MOF. Further
exploration is warranted for Zn²⁺ accumulation into non-target tissues. PEGylated or peptide coatings
(e.g., RGD) for targeting efficiencies against tumors. Co-delivery of immunotherapeutics (e.g., PD-L1
inhibitors). Machine learning for development of optimal linker-metal combinations for precisely
tailored release (Chen et al., 2024). Nanomaterials have changed the concept of diagnostic medicine
with faster, more sensitive, and less invasive detection of disease (Zhang et al., 2023). Their unusual
properties including large surface area, tunable optical properties, and molecular targeting render them
suitable candidates for modern highly sophisticated imaging and biosensing methods (Chen & Smith,
2022).

In comparison with traditional dyes, quantum dots have fluorescence signals 100 times brighter
in medical imaging (Michalet et al., 2005); on the other hand, superparamagnetic iron oxide
nanoparticles provide approximately 40% greater MRI contrast than conventional agents (Weinstein et
al., 2023); moreover, gold nanoparticles act by combining imaging and therapeutic applications with
greater X-ray attenuation in CT while allowing targeting specificity to tumors (Hainfeld et al., 2020).
Gains in biosensing, especially, have been made by nanotechnology, where field effect transistors made
from graphene were able to detect COVID-19 proteins at 0.2 picomolar concentrations - 100 times lower
than standard ELISA tests (Seo et al., 2021).

Gold nanoparticle-based colorimetric assays allow for immediate equipment-free diagnosis via
visible color change (Draz & Shafiee, 2018), whereas surface-enhanced Raman scattering platforms can
detect single molecules (Li et al., 2023). Point-of-care technology that includes nanomaterials, for
example, lateral flow assays and microfluidic chips, advances laboratory-grade testing to the remotest
locations, with some smartphone-based systems detecting at a sensitivity of 1 pg/mL for cardiac
biomarkers (Zheng et al., 2023, ). Some of the newer applications are wearable nanosensors for long-
term monitoring of health (Bandodkar et al., 2021) and AI-based diagnostic platforms that process
nanoparticle-mediated data with 95% accuracy (Chen et al., 2024). Liquid biopsy methods employing
magnetic nanoparticles to isolate tumor-derived exosomes hold out the potential for earlier cancer
detection (Zhang et al., 2023).

Nevertheless, there still exist challenges to be surmounted in enhancing long-term safety (Zhang
et al., 2023), lowering costs, and proceeding through the regulatory routes (FDA, 2021). Future
directions include biohybrid platforms that combine synthetic nanomaterials with biomolecules (Wang
et al., 2024), self-powered autonomous diagnostic devices, and rapid clinical translation of top
15
candidates.Nanodiagnostics is projected to reach the all-time high of the industry by the end of 2027,
which amounts to $25 billion (BCC Research, 2023) reflecting the huge expansion of influence by these
technologies across oncology, cardiology, and infectious disease management domains. Some of the
recent advances are: multiplex detection of biomarkers using quantum dots (Gao et al., 2004), rapid tests
based on gold nanoparticles (Jiang et al., 2022), and health monitoring in real time, with graphene
sensors (Yang et al., 2013).

Such technologies provide fantastic new diagnosis potential. However, there have been concerns
regarding safety about the persistent toxicity they harbor, especially for the chronic use. (Donaldson et
al., 2021). Artificial intelligence to nanodiagnostic platforms is an even more attractive area of research
(Mitragotri et al., 2023), which could significantly facilitate continuous observation of complex
biomarker patterns in real time for early diagnosis and personalized care tracking.

However, as the trends move in this area forward, standardization on characterization methods
(Ehmann et al., 2021) and scaling up will be essential to bring the advances made in the laboratory into
clinically useful products.

16
Chapter 3

MATERIALS AND METHODS

3.1 AI-Integrated Diagnostics

Machine Learning + SERS: Based on SERS spectra, AI algorithms accurately classify tumor
subtypes with 95% accuracy (Chen et al., 2024). Magnetic nanoparticles are used to capture tumor-
derived exosomes in the early detection of cancer (Zhang et al., 2023). Carbon Nanotube Arrays:Real-
time monitoring of Parkinson's patient dopamine (Liu et al., 2023).

3.1.1. Glucose Monitoring Systems

Nanomaterial-based biosensors have revolutionized glucose monitoring for diabetes care.

Continuous glucose monitoring (CGM) systems now include:Enzyme-based sensors: Glucose oxidase
(GOx) immobilized on platinum or gold nanoparticles offers real-time measurements (Wang, 2022).
Non-enzymatic methods: Copper oxide nanowires oxidize glucose directly at reduced potentials (Chen
et al., 2023). Wearable devices: Graphene epidermal skin patches quantify sweat glucose with 94%
accuracy compared to blood tests (Bandodkar et al., 2021). Subcutaneous nanosensors (e.g., Dexcom
G7) now have <10% MARD (Mean Absolute Relative Difference) with 14-day wear duration.

3.2.2. Cancer Biomarker Detection

Nanobiosensors allow early detection of cancer as follows: Liquid biopsy: "Magnetic

nanoparticles detect PD-L1 in the exosomes of cancer cells at 90% agreement with the tissue biopsy"
(Zhang, 2023). Detection of five protein biomarkers in the same time at a concentration of 0.1 pg/mL
(Gao, 2023, Nature Nanotechnology). Silicon nanowires isolate circulating tumor cells (≥5 cells/mL
blood) (Zheng, 2023). The second near-infrared fluorescence imaging (NIR-II, 1000–1700 nm) has
transformed oncologic surgery into providing precise real-time high fluorescence images of tumor
margins. As a common example of this adjustment, the organic dye CH1055-PEG, much like with NIR-I
(700-900nm), saw sufficient imaging depth in preclinical models at 5 mm, with a very good tumor-to-
background ratio (TBR >8) (Zhong et al., 2023).

17
 Deep-tissue visualization: NIR-II light scatters/absorbs much less than visible/NIR-I
wavelengths, allowing detection of subsurface tumors (5-10 mm deep) (Li et al., 2022). Emission of
CH1055-PEG at 1055 nm lessens tissue autofluorescence, rendering the signal clearer. Passive uptake
through the EPR effect, with active targeting being feasible through RGD peptide conjugation (TBR
increases from 5 to 12) (Zhang et al., 2023).PEGylation prolongs circulation time to 4–6 hours while
providing renal clearance, minimizing post-operative retention hazards (FDA-approved PEG molecular
weight < 40 kDa) (Zhong et al., 2023).

Table 3.1: Integration into Clinical Workflow: Steps and Approach (Li et al., 2022).

Procedure Protocol The CH1055-PEG

Pre- Patient
IV administration (2mg/kg) within 24 hours prior to surgery
operative Preparation

Intra- Tumor NIR-II camera (e.g., Hamamatsu ORCA-Fusion) guides

operative Removal excision.

Post- Margin
Ex vivo specimen scanning confirming complete excision
operative Verification

Presently, you will find that there is no FDA-cleared NIR-II imaging system (and today's use is
off-label only). The synthesis of CH1055 remains expensive (~500/mgvs.ICGat500/mgvs.ICGat5/mg).
AI-designed NIR-II dyes (FD-1080, for example) are predicted to penetrate 10 mm (Liu et al., Science
Advances, 2024).

18
Figure 3.1. The proposed plasmonic system, single side resonator, and metallic baffle: transmission
spectra (Jiang & Wang, 2025).

3.2 Therapeutic Applications of Nanomaterials: Drug Delivery Systems

Nanoparticle (NP)-based drug delivery systems have changed perspectives in modern medicine
towards improvement in drug-solubility, bioavailability, and targeted delivery, thereby limiting systemic
toxicity. They may be classified based on three strategies.
3.2.1. Targeted Delivery (Ligand-Functionalized NPs)

Targeting strategies involve surface modification of the nanoparticle through the addition of
targeting ligands such as antibodies, peptides, or aptamers to allow receptor-mediated uptake by
diseased cells.Samples and Possible Uses: Anti-HER2 trastuzumab-conjugated liposomes show 12.3%
accumulation in the tumor versus 0.7% seen for non-targeted NPs (Sukumar et al., 2023). PSMA-
targeted polymeric NPs (for prostate cancer) engineered improved-than-free docetaxel delivery by 8
times (Hrkach et al., 2023). Protein corona formation can veil the targeting ligands (Dobrovolskaia et al.,
2022). Heterogeneous receptor expression in tumors is yet another limit to their universal applicability.

19
Table 3.2: Stimuli-Responsive Release

Trigger Nanoplatform Release Mechanism Application

Degrades at tumor pH Doxorubicin delivery (90% release at

pH ZIF-8 MOFs
(5.0–6.5) pH 5) (Wu et al., 2023)

Thermosensitive
Melts at 40–42°C
Temperature liposomes Localized chemo (e.g., ThermoDox®)
(hyperthermia)
(Lysolipid)

NIR-triggered Photothermal-chemotherapy (Liu et

Light Gold nanoshells
plasmonic heating al., 2022)

Blood-Brain Barrier (BBB) Penetration

Receptor-mediated transcytosis: Angiopep-2-coated NPs bear down's LRP1 receptors (2.5%

brain bioavailability vs. <0.1% for free drugs) (Tian et al., 2022). Cell-penetrating peptides (e.g., TAT)
improve uptake but lack specificity. Nanoformulated paclitaxel (ANG1005): Phase III was launched for
the treatment of brain metastases (NCT03694262). Poor payload delivery efficiency (<5% of injected
dose reaches the brain). Possibility of neurotoxicity caused by nanocarrier materials.

Table 3.3: Comparative Analysis

Approach Advantage Limitation Clinical Stage

High Ligand stability Multiple FDA approvals (e.g.,

Targeted NPs
specificity issues Vyxeos®)

Stimuli- On-demand Requires external

Phase II (ThermoDox®)
Responsive release trigger

BBB-
CNS access Low efficiency Phase III (ANG1005)
Penetrating

20
 Nanoparticle drug delivery systems have been remarkably effective in mollifying the therapeutic
effect in systemic toxicity. Those targeted delivery systems based on ligand-functionalized nanoparticles
have emerged to be particularly promising, as HER2-conjugated polymeric nanoparticles show 12.3%
tumor accumulation with respect to only 0.7% for non-targeted counterparts-an 18-fold improvement in
delivery efficacy (Sukumar et al.,2023).

Recently, there have been enormous strides in the area of stimuli-responsive systems, for
example, pH-sensitive ZIF-8 metal-organic frameworks that can release 90% of their cargo of
doxorubicin at the tumor-pH (5.0) while releasing only 10% at pH 7.4 (physiological pH) for controlled
spatial drug delivery (Wu & Yang, 2023). To negotiate with such tough biological barriers as the blood-
brain barrier, angiopep-2-coated nanoparticles have achieved 2.5% brain bioavailability, 25 times higher
than the free drugs, exploiting the LRP1 receptor-mediated transcytosis (Tian et al.,2022). The systems
are presently being optimized by employing modern strategies such as dual-targeting techniques and AI-
optimized designs, with machine-learning algorithms lately allowing for nanoparticle biodistribution
prediction patterns with 89% accuracy (Wang et al., 2024).

However, there remain a few pertinent challenges-wherein the protein corona effect could
reduce the targeting efficacy by as much as 70% (Dobrovolskaia et al., 2022); and, shallow penetration
depth (usually <5mm) of external stimuli, such as near-infrared light, for stimulus-responsive systems
(Liu et al., 2022). Clinical translation is still on the fast track, with more than 80 FDA-approved
nanomedicines on the market and over 300 in ongoing clinical trials, ranging from oncology to central
nervous system diseases (BCC Research, 2023). The latest advances include the creation of biohybrid
systems that merge synthetic nanoparticles and natural exosomes, which have demonstrated 3-fold
tumor accumulation compared to traditional nanocarriers in preclinical models (Zhang et al., 2023).

The FDA Guidance on Nanotechnology (2021) emphasizes the importance of establishing

standardized characterization protocols and resolving manufacturing issues, allowing for broader clinical
use. The nanomedicine market globally is projected to be $350 billion by 2030, indicating that these
technologies are increasingly affecting the shift of therapeutic paradigms across different disease
indications (Mitragotri et al., 2023).

Case Studies in Nanomedicine

21
 Nanomedicine has brought revolutionary success such as the COVID-19 mRNA-LNP vaccines
(Pfizer-BioNTech/Moderna), wherein lipid nanoparticles (LNPs) facilitated delivery of mRNA with
95% efficiency (Polack et al., 2020). Some of the most important innovations were ionizable lipids for
escape from endosomes and PEGylation for prolonged circulation. More than 10 billion doses were
given by 2023, demonstrating scalability and safety, although anti-PEG antibody (Dobrovolskaia et
al.,2022) and cold-chain requirements are still issues. Another success, Doxil®, cut cardiotoxicity by
50% (Barenholz, JCR, 2012), but its $5,000/dose price and post-generic revenue decline exposed pricing
weaknesses.

On a disheartening note, such disappointments include BIND-014 (PSMA-targeted

nanoparticles), which failed to translate any of its preclinical data into humans for a future trial with <
5% tumor uptake (NCT01812746, 2016). Likewise, CALAA-01 generated massive disappointment as
the first-generation siRNA nanoparticle owing to its immune toxicity and poor tumor penetration
problems (2013), although it would thus inform some subsequent LNP designs such as Alnylam's
Patisiran. These examples draw attention to the need for credible predictive models and combinations
development for nanomedicine.

Successes stem from well-established clinical appropriateness, cost-effective bulk production,

and sound IP. Failures usually result from an over-reliance on animal husbandry or failure to recognize
important biological barriers. The lessons are informing next-generation nanotherapies (improved mode
of targeting, immune stealth).

Table 3.4: Comparative Analysis Success vs. Failure

Factor Success (mRNA-LNP Vaccines) Failure (BIND-014)

Targeting Systemic (no targeting needed) Overestimated PSMA specificity

Manufacturing Scalable microfluidics Complex chemistry

Clinical Need Pandemic urgency Incremental benefit over chemo

Regulatory Path Emergency Use Authorization Conventional FDA process

22
3.3 Nanotheranostics for Cancer

Nanotechnology has further expanded the horizons in cancer treatment approaches by creating
options for targeted therapies with a pro-minimally invasive and prolifically less systemic toxic
outcome. Three kinds of strategy include photothermal therapy (PTT), photodynamic therapy (PDT),
and radio-enhancement therapy (RET), which exploit very specific and unique qualities of
nanomaterials to develop better therapeutic outcomes.

3.1.1. Photothermal Therapy (PTT) with Gold Nanostructures

Gold nanoparticles (AuNPs) convert near-infrared (NIR) light (700–1100 nm) into localized heat
(>50°C), inducing tumor cell apoptosis/necrosis.

Table 3.5: Nanoplatforms & Efficacy

Peak Absorption Photothermal

Nanostructure Size (nm) Tumor Regression Rate
(nm) Efficiency (%)

Gold
120–150 800–820 70–80% 85–90% (murine models)
Nanoshells

Gold Nanorods 40–60 650–900 85–95% 75–80%

Gold
50–70 700–1000 80–90% 70–75%
Nanocages

Photodynamic therapy (PDT) relies on the use of photosensitizers (PSs) that, upon irradiation,
form reactive oxygen species (ROS) to kill cancer cells by triggering apoptosis. Among its main
strengths is that it can mitigate hypoxia in tumors; for example, O₂-releasing nanoparticles such as
MnO₂ have proved to improve PDT performance in hypoxic conditions (Zhang et al., 2023). Also, PDT
can be combined synergistically with other therapies, e.g., photothermal therapy (PTT). For instance,
gold nanoparticle-PS conjugates have shown considerably enhanced tumor regression rates (95% with
PTT together versus only 60% with PDT alone). One strong clinical example of PDT is Foscan®, which

23
is a liposomal mTHPC formulation and has been licensed in Europe for use in the treatment
oropharyngeal cancers.

The Radio-Enhancement Therapy (RET) application is based on a high-atomic number such as

gold and hafnium (for example) involving nanomaterials, increasing the radiation dose to be deposited
in tumors and letting healthy tissues unexposed. In this way, promising results establish the promise of
RET- for instance, this nanoparticle NBTXR3 would amplify the amount of radiation dose absorbed by
tumors around 9 times normal tissue. Studies further demonstrated that gold nanoparticles of about 15
nm in size require a recommended dose of 10-20 mg per gram of the tumor tissue to achieve optimal
radiation enhancement. Nevertheless, a number of disadvantages plague RET, particularly the
uncertainties on long-term retention of heavy metals (Hf, Gd) in the body, raising the need for further
research on safety. Another constraint is the heterogeneous distribution of nanoparticles within the
tumor, leading to uneven delivery of radiation doses and finally diminishing the therapeutic outcome.

Regenerative medicine has been revolutionized by nanotechnology, allowing for precise

regulation of tissue repair mechanisms. Nanoscaffolds that replicate the extracellular matrix (ECM)
offer structural and biochemical signals to direct cell growth. For instance, electrospun polycaprolactone
(PCL) nanofibers (fiber diameter: 200–500 nm) increase stem cell adhesion and differentiation with
80% cell viability against 50% in traditional scaffolds (Sell et al., Biomaterials, 2021). Hybrid scaffolds
containing nanohydroxyapatite (nHA) enhance bone regeneration by mimicking the mineral content of
natural bone, healing 40% faster in critical-size defects (Zhang et al., 2023).

3.1.2. Neural Regeneration Nanomaterials

Restoring neural tissue is still a major problem, but nanomaterials are promising. This carbon
nanotube (CNT) and graphene scaffold enhances neurite outgrowth by 300% with respect to untreated
controls because they possess the conductive character that emulates neuronal signaling (Mazzatenta et
al., 2023). Self-assembling peptide nanofibers, namely RADA16-I, promote an environment conducive
to axon regeneration in spinal cord injury, with approximately 50% return of motor function in
preclinical models (Guo et al., 2022). Nevertheless, long-term biocompatibility and immune response
are still significant challenges.

3.1.3. Bone and Cartilage Repair

24
 Nanomaterials boost bone and cartilage repair by offering bioactive and structural support.
Nanocellulose scaffolds with BMP-2 growth factor promote osteoblast proliferation, closing 90%
defects in rat femur models (Domingues et al., 2023). For cartilage restoration, hyaluronic acid-based
TGF-β3-loaded nanocomposites promote chondrocyte proliferation, repairing 70% of the mechanical
strength of injured joints (Lee et al., 2024). Hyaluronic acid-based TGF-β3-loaded nanocomposites aid
the process of chondrocyte proliferation, repair 70% of injured joints' mechanical strength, and cartilage
restoration (Lee et al. 2024).

Chaotic Picture for the Future of Nanomaterials What could be done is:Becoming ten times more
perfectly immune-compatible in the near future. 3D-templated-imprint fabricated patient-specific
nanoscaffolds. Hydrogogels with effects that can be triggered for on-demand delivery of growth factors.
Favorable scaffold-cell interactive nanomaterials (Mitragotri etal., 2024).

3.4 Antimicrobial Applications of Nanomaterials

An impressive advancement, nanomaterials offer approaches toward combating microbial

infection by three modes of action:

3.4.1. Antibacterial Coatings for Medical Implants

50% of nosocomial infections occur by using these medical devices. A nanocoating provides:
Silver nanoparticle (AgNP) coatings reduce bacterial adhesion by 99% on catheters /implants (Rai et al.,
2023). Broad-spectrum activities against MRSA and E. coli (Kumar et al., 2023). Prevention of bacterial
adhesion for >30 days using quaternary ammonium polymer brushes (Ye et al.,2022).

3.4.2. Antiviral Nanomaterial

Antiviral nanomaterials, and most notably nanoparticles, have become a potential weapon
against viruses in several ways. Gold nanoclusters, for example, were found to block the entry of SARS-
CoV-2 by preventing it from binding with the ACE2 receptor, as seen in a study published in Nature
Nanotechnology in 2023 by Jeremiah et al. Likewise, graphene oxide films display strong antiviral
activities by physically annihilating viral envelopes, with 95% inactivation within five minutes, as
shown by research conducted by Unal et al. in Advanced Science (2023). Also, nanoparticle-formulated
vaccines, like Novavax's Matrix-M™ adjuvant, dramatically boost immune responses, providing better

25
protection against viral infections. These developments reflect the promise of nanotechnology to create
effective antiviral solutions.

3.4.3. Biofilm Disruption Strategies

Nanomaterials provide new ways to destabilize recalcitrant biofilms, which are notoriously
difficult to treat with conventional means. One such strategy includes nitric oxide-releasing
nanoparticles, which penetrate the extracellular polymeric substance (EPS) matrix of biofilms
effectively, resulting in a decrease in biofilm mass up to 85%, as shown by Hetrick et al. Enzymes-
functionalised nanomotors are being pursued as a possible approach for degrading the major matrix
components of the biofilm actively with a 70% removal rate as shown in the study of Soto et al.
published in Science Robotics (2023).

In addition, magnetically guided nanoparticles have the potential of penetrating deep into the
structure of biofilms, thus delivering antibiotics, selecting against the barriers diffusion usually imposes
on the action of drugs. Such nanomaterial-based technology enhances biofilm penetration and
detonation enabling more effective strategies for treating chronic bacterial infections. Nanotechnology,
for instance, allows scientists to design strong agents against infections related to biofilm, which are
now becoming a major problem to healthcare and industry.

26
Chapter 4

RESULTS AND DISCUSSION

Nanomedicines have efficiently entered the realm of clinical translation; more than 80 products
are already approved by the FDA, and over 300 are active trial candidates (Wagner etal, 2023). The
improved efficacy of drugs, reduced toxicity, and patient outcomes contribute to the commercializations.

4.1.Nanomedicines of FDA Approval

A number of nanotherapeutics have made it to clinical use, mainly in oncology and infectious
diseases:

Table 4.1: Key Approved Nanomedicines

Drug (Brand) Nanoplatform Indication Approval Year Sales (2023)

PEGylated Ovarian cancer,

Doxil® 1995 $500M
liposome Kaposi’s sarcoma

Albumin-bound
Breast, pancreatic
Abraxane® paclitaxel (130 2005 $1.2B
cancer
nm)

Liposomal
Onivyde® irinotecan (110 Pancreatic cancer 2015 $350M
nm)

mRNA-LNP Lipid
$30B+
Vaccines nanoparticles COVID-19 2020
(combined)
(Moderna/Pfizer) (70–100 nm)

27
 Hafnium oxide Soft tissue $150M
NBTXR3 (Hensify®) 2023
nanoparticles sarcoma (projected)

There is a significant improvement in reducing unwanted side effects of traditional

chemotherapy by use of nanoparticle-formulated drugs. For example, a reduction of 50% in
cardiotoxicity was seen in Doxil®-liposome-encapsulated doxorubicin compared to free doxorubicin
(Barenholz, 2012). Doxil® encapsulates the drug within a lipid bilayer to protect healthy tissues from
harm while allowing the drug to exert its therapeutic action, making treatment much safer for cancer
patients.

Likewise, Abraxane®, paclitaxel albumin-bound nanoparticle-based formulation, displayed

better clinical benefits in metastatic breast cancer. In a publication by Gradishar in the New England
Journal of Medicine (2020), Abraxane® enhanced the response rate by 30% over traditional taxane-
based therapies. The nanoparticles improve drug solubility as well as enhance tumor targeting with
improved treatment effects and reduced adverse effects. Such progress brings to attention how
nanotechnology is revolutionizing oncology with better drug delivery and patient recovery.

While the promising therapeutic potential of nanomedicine for cancer therapy has long been
recognized, important hurdles must be overcome before clinical translation can become a reality. Chief
among these challenges is the low tumor accumulation of nanoparticles, less than 5% of the injected
dose generally being deposited in the target site, as pointed out by Wilhelm et al. in Nature Reviews
Materials (2016). Such an ineffective biodistribution limits therapeutic outcome and jeopardizes possible
off-target toxicity, thus necessitating improved delivery systems that would optimize tumor penetration
and retention.

Another important hurdle is immune recognition which could inhibit the efficacy of
nanotherapies.For instance, induction of anti-PEG antibodies in a patient-this omnipresent stealth-
coating agent-has been demonstrated to reduce clinical efficacy and circulation time of nanoparticles, as
reported by (Dobrovolskaia et al. 2022). Such immune recognition has the potential to cause rapid
clearance of nanomedicine and thus make them therapeutically inconsequential. Overcoming these
biodistribution and immunological hurdles is thus a sine qua non for the next frontier in particle-based
therapy.

28
 Nanomedicine is witnessing a revolutionary change with the emergence of LNPs as the leading
platform for drug delivery. At this time, approximately 60% of all nanodrugs in development (2024) are
attributed to LNPs, fueled by their success with mRNA vaccines and the ability to formulate different
therapeutics. Their biocompatibility, scalable manufacturing, and tissue-specific targeting led to the
assertion of LNPs as the preeminent force of nanomedicine innovation.

Table 4.2: Market Segmentation (2024 vs. 2030 Forecast)

2024 Market 2030

Segment Key Drivers
Size Projection

Oncology $75B $180B Targeted chemo, immunotherapy NPs

Infectious
$50B $90B mRNA vaccines, antiviral NPs
Diseases

CNS Disorders $10B $35B BBB-penetrating NPs (e.g., Alzheimer’s)

Cardiovascular $8B $25B Nanofiber stents, siRNA therapies

In the future, biohybrid systems, specifically exosome-based therapies, are set to disrupt the
industry. These nanocarriers naturally derived from bioresources provide greater biocompatibility, lower
immunogenicity, and inherent tissue-targeting abilities, making them set to reign supreme by 2030.
Artificial intelligence is meanwhile speeding along developments, with machine learning algorithms
optimizing nanomedicine formulation. In ACS Nano, a study published in 2023 by Mitragotri et al.
demonstrated how AI-assisted design can decrease development times by 40% and accelerate
optimization of nanoparticle properties like stability, drug loading, and biodistribution. All of these are
leading to a new era of smarter, better nanomedicine development.

Commercialization of nanomedicines is confronted with several key challenges, such as

complexity in manufacture, with the elevated cost of Good Manufacturing Practice (GMP)-regulated
nanoparticle production prohibiting scalability. Also, regulatory ambiguity exists from the absence of
well-established characterization protocols, as identified by the FDA in 2021, which creates issues
around approval pathways.Another major apprehension would be the so-called patent cliff effect; the

29
instant Doxil® came off patent in 2019, generic competition ravaged brand revenue of 70%, revealing
the financial instability of nanodrug development.

4.2. Safety and Ethical Considerations in Nanomedicine

Despite nanomedicine having enormous therapeutic and diagnostic prospects, translation to the
clinic requires stringent safety hazard evaluation, immune interaction evaluations, regulatory
implications, and ethical matters with patient privacy being of the utmost importance.

4.2.1. Evaluation of Nanotoxicity

NPs can induce toxicity through a plethora of mechanisms. One mechanism is the generation of
ROS by metal oxide NPs like TiO₂ and ZnO, inducing oxidative stress in liver and kidney cells (Zhang
et al.,2023). Non-degradable NPs such as gold and quantum dots long-term accumulation in organs with
possible chronic exposure is another concern (Donaldson et al., 2021). Size-related effects are the
biggest concern—NPs with a size less than 10 nm are capable of penetrating biological barriers, that is,
placenta and blood-brain barrier (FDA, 2021 Guidance), which will need scrupulous safety evaluation.

Table 4.3 Testing Strategies

Method Purpose Example

In vitro assays Cytotoxicity screening MTT assay for cell viability

In vivo models Organ-specific toxicity Murine liver/kidney histopathology

Computational models Predictive toxicology Nano-QSAR for risk assessment

4.2.2. Immune System Interactions

Nanoparticles (NPs) interact with the immune response on complex and sometimes quite
unpredictable levels. Some of the biggest problems involve triggering complement activation, with
PEGylated liposomes inducing anti-PEG antibodies in around 40% of patients, thus compromising the
efficacy of drugs and increasing clearance rates (Dobrovolskaia et al.,2022). Macrophage clearance also
remains a major hurdle, with more than 90% of injected NPs being quickly cleaned out from circulation
30
by RES before they can reach the target site (Wilhelm et al., 2016). Induced immunomodulatory action-
certainly gold nanoparticles (AuNPs) can suppress the inflammatory state in arthritis but will probably
also compromise defenses against infections (Tsoi et al., 2023).

To counter these immune responses, scientists are innovating sophisticated means. Stealthy
coatings, such as polyzwitterions, have shown excellent reduction in protein adsorption, outperforming
conventional PEG coatings (Zhang et al., 2024). An alternative method encompasses biomimetic
nanoparticles, wherein cell membrane concealment is applied to avoid being detected by the immune
system while increasing circulation duration (Chen et al., 2023).

4.2.3. Challenges from regulatory bodies

Regulatory agencies worldwide are confronted with specific challenges in assessing and
approving nanomedicines. There are no universally accepted, standardized testing protocols for
nanoparticles with regard to safety assessment, biodistribution and long-term effect evaluation, which
make the approval process challenging. Nanomaterials are rather complex as small differences in size,
shape, and surface chemistry can have dramatic effects on biology-they need additional
characterizations as opposed to conventional drugs. However, regulatory agencies also need to deal with
issues of immune interactions, possible toxicity, environmental effect, and, above all, ensuring that
innovation is kept on track in a rapidly developing sector.

The importance of patient privacy and data protection is brought to light with the rise of
nanodiagnostics. Implementation of wearable nanosensors like graphene-based electronic tattoos creates
continuous real-time updates that leave cloud servers vulnerable to cybersecurity infiltrations
(Bandodkar et al., 2021). Nanoparticle-assisted liquid biopsies also help in cancer mutation detection
with high sensitivity, which, according to HIPAA and GDPR laws, would require strict safeguards of
genetic privacy. Thus, AI-based nanodiagnostics will also be able to predict diseases even before
symptoms develop, which can lead to ethical dilemmas around patient consent, insurance bias, and
psychological impact. "Towards these challenges," say the quoted scientists, "we propose blockchain
encryption for all the nano-sensor data transmissions" (Liu et al., 2023) and very strict anonymization
protocols applied to genomic data gathered through nanodiagnostic testing. Should these measures not
be instituted properly, the gain from these next-generation diagnostics may well be outweighed by
privacy threats and ethical issues.

31
4.3. Up-To-Date Issues with Nanomedicine Development and Translation

Although nanomedicine has the potential to transform medicine, scalability, manufacturing, and
clinical translation are major challenges. Batch-to-batch consistency of nanoparticle characteristics—
size, surface charge, and drug load—are critical (e.g., ±5% size uniformity for liposomal drugs is
required for FDA approval).Microfluidics-derived biopolymeric nanoparticles (LNPs) also hinder their
large-scale manufacturing by their complicated synthesis protocols. Such conditions delay the
commercialization procurement and increase costs, thus restricting the patient's accessibility to advanced
nanotherapies. Advances in process automation and quality control technologies will solve these
debottlenecking issues, including aspects of regulatory harmonization to enable reproducible and
scalable production of nanomedicines.

4.3.1. Efficiency in Targeted Delivery

Ironically, one of the most persistent problems of nanomedicine is delivering nanoparticles with
low targeting efficacy. Research has found that less than 5% of injected nanoparticles reach into target
tissues-more are cleared by the liver and spleen or accumulate in off-target organs (Wilhelm et al.,
2016). Less cell biodistribution greatly impedes therapeutic action, enhancing probable side effects.

Consider a rapid protein corona formation-a layer of proteins and other biomolecules on
nanoparticles initiated by an intravenous administration occurring in minutes. The formation is dynamic,
modifying surface properties of the nanoparticles, typically masking targeting ligands and redirecting
particles from the intended destination. Thus, overcoming biological barriers will require innovations in
stealth coatings, active targeting methods, and predictive modeling of nanoparticle behavior in the
physiological environment.

4.3.2. Improved Innovations for Delivery

Recent advances in nanomedicine are showing novel approaches which can be brought forward
in their efforts to overcome delivery barriers. For example, DNA origami carriers are possibly
programmable for spatial and temporal precision in the release of drugs (Li et al., 2023). At the same
time, superparamagnetic iron oxide nanoparticles (SPIONs) could be placed under MRI guidance for
real-time navigation of therapeutic cargo to the location of interest, partially overcoming some
biodistribution barriers.

32
4.3.2. Cost-Effectiveness Thresholds

The most significant challenges on the path to economic sustainability pertaining to

nanomedicines come in the form of research and development costs. To develop a nanodrug currently
requires an investment of approximately $300 million. This is three times the price of $100 million that
a conventional drug usually costs. Extreme pricing pressures also affect the industry, as witnessed with
the case of Doxil® when its price dropped by 80% due to the availability of a generic product. These
financial constraints put pressure on the need for more efficient manufacturing processes along with
technology scalable and innovative reimbursement schemes to bridge patient access while maintaining
incentives for sustainable development.

The business of nanomedicine is steeped in the intersectionality of technologies responsible for

precision and easy scaling. AI-enabled automation of nanoparticles has sped the optimization processes
for formulations with reduced human errors. In parallel, advancements in personalized nanomedicine
might allow for the potential delivery of customized therapies for specific patients through point-of-care
fabrication of 3D printed nanocarriers. To further reduce barriers, global collaboration frameworks—
such as co-owned GMP production facilities—can democratize access to nanomedicine production
capacity.

4.4 Future Perspectives in Nanomedicine

The upcoming decade will usher in revolutionary leaps in nanomedicine, powered by AI,
theranostics, precision methods, and bioelectronic integration. They are designed to transcend existing
restraints in drug delivery, diagnosis, and treatment based on individuals.

4.4.1. AI-Designed Nanomedicines

Existing development processes are still inefficient, based on trial-and-error screening of 1,000+
formulations per drug. Moreover, there are still gaps in the knowledge of nanoparticle-bio interactions,
such as protein corona formation and immune clearance mechanisms. AI-driven design provides a
solution by predicting optimal nanoparticle properties—size, charge, and surface chemistry—to achieve
maximum targeting and minimum side effects. Machine learning algorithms tuned on large data sets
might speed nanocarrier design optimization while revealing new, unknown biological interactions,
leading to a new generation of smart nanomedicine.

33
 Theragnostic nanoplatforms are a new category of convergent systems with real-time diagnostic
imaging functions coupled with site-specific therapeutic delivery. Leading Examples & Advantages:
Such intelligent systems facilitate real-time monitoring of treatments—e.g., modulating photothermal
therapy (PTT) laser intensity in response to live near-infrared (NIR) imaging feedback.Another exciting
development is closed-loop delivery of drugs; for example, glucose-sensitive nanoparticles dynamically
release insulin based on blood glucose concentrations, simulated to behave like the pancreas.

Best – "With great promise, there comes complexity in terms of regulation (they usually
represent drug-device combinations with dual approval pathways) and the cost of multimodal imaging
devices required to adopt these clinically."

Personalized Nanomedicine: Individualizing Treatment Approaches

Autologous exosome-encapsulating nanoparticles, produced from a patient's own biopsies of

tumors, facilitate enhanced targeting as well as minimize immunogenicity (Zhang et al., 2023). At the
same time, *3D-printed implants with programmable release profiles of nanodrugs* enable precise
dosing scaled to disease dynamics. CRISPR-delivering nanoparticles can fix single-point mutations (e.g.
cystic fibrosis) while liquid biopsy-guided systems dynamically modify drug payloads from circulating
tumor DNA profiles. Personalized nanomedicine has shown a 60% enhanced rate of therapeutic
response over conventional "one-size-fits-all" nanotherapies (BCC Research, 2024), thus holding
promise in re-defining precision medicine.

However, there remain problems with mass production and cost-effectiveness to make it viable
on a large scale. All these developments are leading to a time when nanomedicine will transition from
blanket treatment to adaptive, patient-specific therapy—though, hurdles at the cost and regulatory levels
will be necessary to overcome for clinical translation. Innovations in nanotechnology are expected to
bring about self-powered systems and move us a step closer to bioelectronics frontiers. Biomimetics
such as piezoelectric nanoparticles can change the implantable medicine paradigm by utilizing
biomechanical energy-in-the-course-from an organ's motions, such as vibrations due to heartbeats, for
automatic powering of a drug-delivering device or sensing capability. Meanwhile, advances in brain-
machine interfaces (BMIs) exploit ultra-thin graphene nanoelectrodes to provide unparalleled resolution
of neural signals, hence paving the way for real-time thought decoding for prosthetic control or
cognitive therapy.

Ethical Considerations in Advanced Nanomedicine

34
 The advent of long-lasting nanodevices raises fundamental ethical issues: Implantable
nanosystems that are gathering sensitive neural or physiological information need to be encrypted at
military levels to avoid hacking or unauthorized retrieval.The understanding of bio compatibility over
the long run and not only the safety of chronic neural implants such as inflammation or degradation of
material is limited; it needs further critical post-market surveillance. Such technologies actually bring
the line between treatment and enhancement into a new dimension, thus necessitating the establishment
of new ethical paradigigms to go with consent, privacy, and fairness of access for networked
nanomedicine.

35
Chapter 5

CONCLUSION

Nanomedicine has become one of the most revolutionary drivers of healthcare in contemporary
times, reconciling scientific progress and clinical fact. From the miraculous success of mRNA-LNP
vaccines that rescued millions during the COVID-19 pandemic to the accuracy of targeted nanotherapies
for cancer, nanoparticles have revolutionized drug delivery, diagnostics, and regenerative medicine.
However, as we are at the forefront of this revolution, we must also recognize the challenges that lie
ahead—scalability, immune recognition, regulatory challenges, and ethical concerns—that must be
addressed with great urgency.

Where Nanomedicine Has Redefined Medicine Nanoparticles have overcome previously

impenetrable biological barriers. Liposomal doxorubicin (Doxil®) proved that toxicity could be reduced
without loss of effectiveness, and HER2-targeted nanocarriers showed that tumors could be targeted
selectively. The mRNA-LNP vaccines, the pièce de résistance, showed how nanotechnology could make
possible quick, worldwide responses to pandemics. Quantum dots and gold nanoparticles have made
single-molecule detection a reality, while wearable nanosensors now enable real-time monitoring of
health. Liquid biopsy platforms with magnetic nanoparticles are making early detection of cancer a
reality.

Combining therapy and diagnostics has given rise to a new era of personalized medicine.
Hafnium oxide nanoparticles (NBTXR3) not only boost radiotherapy but also enable precise imaging of
the treatment area. Even as nanomedicines succeed in so many ways, the area has key challenges: Few
nanomedicines are successfully scaled up from the laboratory to the marketplace due to batch-to-batch
variations and production costs. Although PEGylation prolongs circulation time, anti-PEG immunity has
the potential to make therapies futile. Regulators are perplexed about how to categorize nanotherapies—
are they drugs, devices, or something new? Who does the data from implantable nanosensors belong to?
How can we avoid abuse of AI-compiled nanodrugs?

36
Chapter 6

SUMMARY

AI and Machine Learning will enable faster nanomedicine design, forecasting best formulations
in days instead of years. Biohybrid Systems (for example, exosome-coated nanoparticles) will improve
biocompatibility and targeting. Personalized Nanomedicine will reign supreme, with therapies specific
to a person's genetic and metabolic makeup. Self-Regulating Nanosystems will be developed, which will
deliver drugs only upon the detection of disease biomarkers.

The future of nanomedicine rests on collaboration between disciplines—material scientists,

clinicians, regulators, and ethicists need to collaborate to overcome the limitations of today. As we
advance towards nanorobotics, brain-machine interfaces, and programmable therapeutics, we need to
make sure that these developments are safe, equitable, and accessible to everyone.

Nanomedicine is not just the future—it is the present, reshaping medicine one nanoparticle at a
time. The question is no longer if nanotechnology will transform healthcare, but how quickly we can
address the remaining challenges to unlock its full potential. The speed of integration of nanomaterials
into mainstream healthcare has increased rapidly, while the prospect of solving apparently incurable
medical problems by unique physicochemical properties and multifunctionalizations of their materials
continues to unfold.

37
Chapter 7

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