Photodynamic Therapy and the Use of Upconversion Nanoparticles

Nanoscale, 2014

Elucidation of upconversion nanoparticles (UCNPs) that can be excited by nearinfrared (NIR) light is an interesting topic in the field of photodynamic therapy (PDT). However, the PDT efficiency of conventional UCNPs is limited due to the low quantum yield and overheating effect of the 980 nm light source. In this study, a light source with a wavelength of 808 nm was used as an excitation source for Nddoped UCNPs to solve the overheating effect. UCNPs with a core@shell structure (NaYF 4 :Yb,Er,Nd@NaYF 4 :Yb,Nd) were synthesized to increase the upconversion emission efficiency. Dual-color emitting Er-doped UCNPs and dual photosensitizers (Chlorin e6 and Rose Bengal) were used for enhanced PDT. Each photosensitizer could absorb red and green emissions of the UCNPs to generate reactive oxygen species (ROS), respectively. The ROS generation in a dual photosensitizer system is significantly higher than that in a single photosensitizer system. Additionally, PDT induces immunogenic apoptosis. In this study, by utilizing a highly efficient PDT agent, PDT-induced apoptosis was studied by biomarker analysis.

Nanomaterials

Photodynamic therapy (PDT) is a minimally invasive cancer modality that combines a photosensitizer (PS), light, and oxygen. Introduction of new nanotechnologies holds potential to improve PDT performance. Upconversion nanoparticles (UCNPs) offer potentially advantageous benefits for PDT, attributed to their distinct photon upconverting feature. The ability to convert near-infrared (NIR) light into visible or even ultraviolet light via UCNPs allows for the activation of nearby PS agents to produce singlet oxygen, as most PS agents absorb visible and ultraviolet light. The use of a longer NIR wavelength permits light to penetrate deeper into tissue, and thus PDT of a deeper tissue can be effectively achieved with the incorporation of UCNPs. Recent progress in UCNP development has generated the possibility to employ a wide variety of NIR excitation sources in PDT. Use of UCNPs enables concurrent strategies for loading, targeting, and controlling the release of additional drugs. In this review article, recent progress in the development of UCNPs for PDT applications is summarized.

Optics Express, 2009

We present a novel process for the production of three-layer Composite Nanoparticles (CNPs) in the size range 100-300 nm with an upconverting phosphor interior, a coating of porphyrin photosensitizer, and a biocompatible PEG outer layer to prevent clearance by the reticuloendothelial system. We show that these CNPs produce millimolar amounts of singlet oxygen at NIR intensities far less than other two-photon techniques.

Analyst, 2010

Upconversion refers to non-linear optical processes that convert two or more low-energy pump photons to a higher-energy output photon. After being recognized in the mid-1960s, upconversion has attracted significant research interest for its applications in optical devices such as infrared quantum counter detectors and compact solid-state lasers. Over the past decade, upconversion has become more prominent in biological sciences as the preparation of high-quality lanthanide-doped nanoparticles has become increasingly routine. Owing to their small physical dimensions and biocompatibility, upconversion nanoparticles can be easily coupled to proteins or other biological macromolecular systems and used in a variety of assay formats ranging from bio-detection to cancer therapy. In addition, intense visible emission from these nanoparticles under near-infrared excitation, which is less harmful to biological samples and has greater sample penetration depths than conventional ultraviolet excitation, enhances their prospects as luminescent stains in bio-imaging. In this article, we review recent developments in optical biolabeling and bio-imaging involving upconversion nanoparticles, simultaneously bringing to the forefront the desirable characteristics, strengths and weaknesses of these luminescent nanomaterials.

International Journal of Nanomedicine, 2019

Nanomedicine is a medical application of biochemistry incorporated with materials chemistry at the scale of nanometer for the purpose of diagnosis, prevention, and treatment. New models and approaches are typically associated with nanomedicine for precise multifunctional diagnostic systems at molecular level. Hence, employing nanoparticles (NPs) has unveiled new opportunities for efficient therapies and remedy of difficult-to-cure diseases. Among all types of inorganic NPs, lanthanide-doped up-conversion nanoparticles (UCNPs) have shown excellent potential for biomedical applications, especially for multimodal bioimaging including fluorescence and electron microscopy. Association of these visualization techniques plus the capability for transporting biomaterials and drugs make them superior agents in the field of nanomedicine. Accordingly, in this review, we firstly presented a fundamental understanding of physical and optical properties of UCNPs and secondly, we illustrated some of the prominent associations with bioimaging, theranostics, cancer therapy, and optogenetics.

Scientific Reports, 2015

Core-shell nanoparticles (CSNPs) with diverse chemical compositions have been attracting greater attention in recent years. However, it has been a challenge to develop CSNPs with different crystal structures due to the lattice mismatch of the nanocrystals. Here we report a rational design of core-shell heterostructure consisting of NaYF 4 :Yb,Tm upconversion nanoparticle (UCN) as the core and ZnO semiconductor as the shell for potential application in photodynamic therapy (PDT). The core-shell architecture (confirmed by TEM and STEM) enables for improving the loading efficiency of photosensitizer (ZnO) as the semiconductor is directly coated on the UCN core. Importantly, UCN acts as a transducer to sensitize ZnO and trigger the generation of cytotoxic reactive oxygen species (ROS) to induce cancer cell death. We also present a firefly luciferase (FLuc) reporter gene based molecular biosensor (ARE-FLuc) to measure the antioxidant signaling response activated in cells during the release of ROS in response to the exposure of CSNPs under 980 nm NIR light. The breast cancer cells (MDA-MB-231 and 4T1) exposed to CSNPs showed significant release of ROS as measured by aminophenyl fluorescein (APF) and ARE-FLuc luciferase assays, and ,45% cancer cell death as measured by MTT assay, when illuminated with 980 nm NIR light.

Frontiers in Chemistry, 2022

Biomedicines, 2021

Due to the unique properties of lanthanide-doped upconverting nanoparticles (UCNP) under near-infrared (NIR) light, the last decade has shown a sharp progress in their biomedicine applications. Advances in the techniques for polymer, dye, and bio-molecule conjugation on the surface of the nanoparticles has further expanded their dynamic opportunities for optogenetics, oncotherapy and bioimaging. In this account, considering the primary benefits such as the absence of photobleaching, photoblinking, and autofluorescence of UCNPs not only facilitate the construction of accurate, sensitive and multifunctional nanoprobes, but also improve therapeutic and diagnostic results. We introduce, with the basic knowledge of upconversion, unique properties of UCNPs and the mechanisms involved in photon upconversion and discuss how UCNPs can be implemented in biological practices. In this focused review, we categorize the applications of UCNP-based various strategies into the following domains: neuromodulation, immunotherapy, drug delivery, photodynamic and photothermal therapy, bioimaging and biosensing. Herein, we also discuss the current emerging bioapplications with cutting edge nano-/biointerfacing of UCNPs. Finally, this review provides concluding remarks on future opportunities and challenges on clinical translation of UCNPs-based nanotechnology research.

Materials, 2022

Upconverting luminescent nanoparticles (UCNPs) are “new generation fluorophores” with an evolving landscape of applications in diverse industries, especially life sciences and healthcare. The anti-Stokes emission accompanied by long luminescence lifetimes, multiple absorptions, emission bands, and good photostability, enables background-free and multiplexed detection in deep tissues for enhanced imaging contrast. Their properties such as high color purity, high resistance to photobleaching, less photodamage to biological samples, attractive physical and chemical stability, and low toxicity are affected by the chemical composition; nanoparticle crystal structure, size, shape and the route; reagents; and procedure used in their synthesis. A wide range of hosts and lanthanide ion (Ln3+) types have been used to control the luminescent properties of nanosystems. By modification of these properties, the performance of UCNPs can be designed for anticipated end-use applications such as phot...

Particle & Particle Systems Characterization, 2019

render them particularly useful in many biological applications including multimodal in vivo biological imaging, [4,7] biodetection, [8,9] clinical diagnosis, [10] and drug/gene delivery (Figure 1). [4] UCNPs enable the conversion of NIR photons of low-energy into visible or ultraviolet (UV) photons of high-energy via photon upconversion process. [11] The concept of photon upconversion is developed from anti-Stokes emission process generated by upconverting luminescent materials. In conventional host luminescent nanomaterials, anti-Stokes emission is generated through simultaneous twophoton absorption (STPA) and second harmonic generation (SHG). [12-15] These photon absorption processes need an ultrashort pulse laser (e.g., femtosecond pulse laser) with extremely high exciting power-density (10 6-10 9 W cm −2) to produce large numbers of excitation photons and, the use of such a pulse laser is very expensive. [1,16,17] Another drawback is the use of noncentrosymmetric molecular structure with a weak D-π-A configuration (D: donor, A: acceptor) that results in low twophoton absorption (TPA) capacity. [12,15] Many efforts have been made to enhance the TPA capacity by optimizing the atomic or molecular structure, which includes conformation rigidity, strong π-conjugation, and incorporation of electron donors and acceptor atoms on a π-conjugated structure. [18] However, the excitation power-density is still high to produce sufficient photons essential for the process. The most popular and attractive alternative for the generation of anti-Stokes emission is an upconversion emission process induced by doping of trivalent transition metals such as rare-earth (RE) trivalent lanthanide ions (Ln 3+) on the host luminescent material. [19-21] Unlike STPA and SHG processes, it is a nonlinear anti-Stokes emission process in which a sequential, rather than simultaneous, absorption of two or more low-energy photons (longer wavelength) occurs leading to the emission of high-energy photons (short wavelength). [22-25] The fundamental concept of upconversion was first proposed by the physicist N. Bloembergen in 1959. His idea was to construct a solid-state IR counter device capable of counting IR photons through their interaction with a solid inorganic matrix (upconverting materials). [26] Later in the mid-1960s, the process of upconversion was first discovered by Auzel, [22] and rapidly became popular for the emission of large anti-Stokes shifts (up to 500 nm), sharp emission bandwidths (10-20 nm full-width Upconversion nanoparticles (UCNPs) convert low-energy infrared (IR) or near-infrared (NIR) photons into high-energy emission radiation ranging from ultraviolet to visible through a photon upconversion process. In comparison to conventional fluorophores, such as organic dyes or semiconductor quantum dots, lanthanide-ion-doped UCNPs exhibit high photostability, no photoblinking, no photobleaching, low cytotoxicity, sharp emission lines, and long luminescent lifetimes. Additionally, the use of IR or NIR for excitation in such UCNPs reduces the autofluorescence background and enables deeper penetration into biological samples due to reduced light scattering with negligible damage to the samples. Because of these attributes, UCNPs have found numerous potential applications in biological and medicinal fields as novel fluorescent materials. Different upconversion mechanisms commonly observed in UCNPs, various methods that are used in their synthesis, and surface modification processes are discussed. Recent applications of Ln-UCNPs in the biological and medicinal fields, including in vivo and in vitro biological imaging, multimodal imaging, photodynamic therapy, drug delivery, and antibacterial activity, are also presented.