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Activation of photosensitive proteins with Radioluminescent nanoparticles and X-rays

Grant number: 18/13016-6
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): October 01, 2018
Effective date (End): January 31, 2021
Field of knowledge:Biological Sciences - Biophysics
Principal Investigator:Antonio José da Costa Filho
Grantee:Mariana Chaves Micheletto
Home Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Photodynamic Therapy (PDT) has gained relevance due to its applications in cancer treatments and has now stood out for its variety of applications, such as in the fight against neoplastic diseases, inflammatory diseases, microbial infections and the fight against aging. PDT is a technique based on the use of three essential components: light, a photosensitizing molecule and oxygen. When exposed to light of adequate wavelength, the photosensitizing molecule is capable of producing reactive oxygen species from molecular oxygen. The discovery and development of phototoxic proteins capable of producing reactive oxygen species aligned with the development of Optogenetics makes it possible to use genetically encoded photosensitizers, increasing the specificity of the treatment. However, when it comes to in vivo use, optical techniques are limited by the low penetration of UV-visible light into biological tissues. To overcome this limitation, this project proposes the use of X-rays, due to their penetrability in soft tissues, as energy source of excitation of photosensitive proteins. Given the low interaction of X-rays with proteins, it will be necessary to use radioluminescent nanoparticles, capable of converting the energy of ionizing radiation into photons of UV-visible light. In addition to enabling deep tumor therapy in view of the high penetration of high energy photons in the tissue, the use of X-rays as a source of light in PDT makes it possible to integrate diagnostic, radiotherapy and PDT for theranostic applications. In this differentiated approach, not only can the tumor cure rate be increased, but the radiation dose and side effect in radiotherapy can also be decreased.