Presentation Title: Bilirubin-Coated Radio-Luminescent Particles for Radiation-Induced Photodynamic Therapy
Author Name(s): Dhushyanth Viswanath
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 (RT) have shown clinical promise in several cancers but are limited again by light penetration and the need for selective photosensitization of the treatment area. We report the development of bilirubin-photodynamic nanoparticles (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 radio-luminescent properties of their CaWO4 nanoparticle cores. PEG-BR/CWO NPs facilitate a combination of PDT and radiation therapy and represent a previously unexplored application of PEG-bilirubin conjugates as a photosensitizing agent. 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 in vitro and in murine xenograft models of head and neck cancer. The results of our studies indicate that PEG-BR/CWO NPs are promising agents for facilitating combined RT-PDT in deep-seated tumors.
Pizzuti, V.; Viswanath, D.; Torregrosa-Allen, S. E.; Currie, M. P.; Elzey, B. D.; Won, Y.-Y., Bilirubin-Coated Radio-Luminescent Particles for Radiation-Induced Photodynamic Therapy. ACS Applied Bio Materials 2020.