Recent Progress and Trends in X-ray-Induced Photodynamic Therapy with Low Radiation Doses

Abstract

The prominence of photodynamic therapy (PDT) in treating superficial skin cancer inspires innovative solutions for its congenitally deficient shadow penetration of the visible-light excitation. X-ray-induced photodynamic therapy (X-PDT) has been proven to be a successful technique in reforming the conventional PDT for deep-seated tumors by creatively utilizing penetrating X-rays as external excitation sources and has witnessed rapid developments over the past several years. Beyond the proof-of-concept demonstration, recent advances in X-PDT have exhibited a trend of minimizing X-ray radiation doses to quite low values. As such, scintillating materials used to bridge X-rays and photosensitizers play a significant role, as do diverse well-designed irradiation modes and smart strategies for improving the tumor microenvironment. Here in this review, we provide a comprehensive summary of recent achievements in X-PDT and highlight trending efforts using low doses of X-ray radiation. We first describe the concept of X-PDT and its relationships with radiodynamic therapy and radiotherapy and then dissect the mechanism of X-ray absorption and conversion by scintillating materials, reactive oxygen species evaluation for X-PDT, and radiation side effects and clinical concerns on X-ray radiation. Finally, we discuss a detailed overview of recent progress regarding low-dose X-PDT and present perspectives on possible clinical translation. It is expected that the pursuit of low-dose X-PDT will facilitate significant breakthroughs, both fundamentally and clinically, for effective deep-seated cancer treatment in the near future.