Bilirubin-Coated Radioluminescent Particles for Radiation-Induced Photodynamic Therapy

Abstract

Photodynamic therapy (PDT) has shown potential as a cancer treatment modality, but its clinical application is limited due to its visible-light activation since visible wavelengths of light cannot penetrate tissues well. Additionally, combination therapies utilizing PDT and radiotherapy have shown clinical promise in several cancers but are limited again by light penetration and the need for selective photosensitization of the treatment area. Herein, we report the development of bilirubin-photodynamic nanoparticles (PEGylated bilirubin-encapsulated CaWO4 nanoparticles or “PEG-BR/CWO NPs”). PEG-BR/CWO NPs are a formulation of PEGylated bilirubin micelles encapsulating CaWO4 nanoparticles. These particles are capable of activating PDT via X-ray irradiation within deep tissues due to the radioluminescence properties of their CaWO4 nanoparticle cores. PEG-BR/CWO NPs facilitate a combination of photodynamic and radiation therapy and represent a previously unexplored application of PEG-bilirubin conjugates as photosensitizing agents. When irradiated by X-rays, PEG-BR/CWO NPs emit UV-A and visible light from their CaWO4 cores, which excites bilirubin and leads to the production of singlet oxygen. PEG-BR/CWO NPs exhibit improvements over X-ray therapy alone in vitro and in murine xenograft models of head and neck cancer. The data presented in this study indicate that PEG-BR/CWO NPs are promising agents for facilitating combined radio-photodynamic therapy in deep tissue tumors.

Pilot-Scale Optimization of the Solvent Exchange Production and Lyophilization Processing of PEG–PLA Block Copolymer-Encapsulated CaWO4 Radioluminescent Nanoparticles for Theranostic Applications

“…The final solid was dried overnight in a vacuum oven at room temperature. The mean diameter of CWO NPs was measured to be approximately 33 nm by transmission electron microscopy (TEM). , …”

“…For example, chemotherapeutic drugs, such as paclitaxel, have been extensively studied in the context of polymeric NP encapsulations . Furthermore, significant research has been conducted to study the potential of inorganic materials such as gold, silver, iron oxide, and calcium tungstate (CaWO 4 or CWO for short) NPs in biomedical imaging and treatment applications. − …”

“…Because CWO NPs tend to agglomerate in aqueous physiological environments, it becomes necessary to encapsulate the NPs within a BCP micelle, such as one that is composed of hydrophilic PEG and hydrophobic PLA. Through an established solvent exchange method, the CWO NPs can be encapsulated into the polymeric micelles, making them suitable for intratumoral administration, as seen in Figure . , …”

Promoting Reactive Oxygen Species Generation: A Key Strategy in Nanosensitizer-Mediated Radiotherapy

“…Some semiconductor nanomaterials containing high-Z elements also show their potential in radiosensitization, among which alkaline earth metal tungstates are representative nanosensitizers [91]. Jo et al confirmed the radiosensitization effect of CaWO 4 NPs both in vitro (head and neck cancer cells) and in vivo (xenografts) [92].…”

Recent Advances in Photodynamic Therapy for Deep-Seated Tumors with the Aid of Nanomedicine

“…Diverse radiation-sensitive materials, including CaWO 4 NPs, SrAl 2 O 4 :Eu 2+ NPs, Cu NPs, Au nanorods, and Au 8 nanocrystals, constructed by mid- or high-Z elements showed potential in X-ray-triggered persistent luminescence-mediated PDT [ 48 , 49 , 50 , 51 , 52 ]. Deng et al proposed a platform using PLGA vesicles to carry PS verteporfin and gold NPs (2–5 nm) together for efficient energy transfer between the PS and Au NPs.…”