X-ray induced photodynamic therapy with copper-cysteamine nanoparticles in mice tumors

Abstract

Photodynamic therapy (PDT), a treatment that uses a photosensitizer, molecular oxygen, and light to kill target cells, is a promising cancer treatment method. However, a limitation of PDT is its dependence on light that is not highly penetrating, precluding the treatment of tumors located deep in the body. Copper-cysteamine nanoparticles are a new type of photosensitizer that can generate cytotoxic singlet oxygen molecules upon activation by X-rays. In this paper, we report on the use of copper-cysteamine nanoparticles, designed to be targeted to tumors, for X-ray–induced PDT. In an in vivo study, results show a statistically significant reduction in tumor size under X-ray activation of pH-low insertion peptide–conjugated, copper-cysteamine nanoparticles in mouse tumors. This work confirms the effectiveness of copper-cysteamine nanoparticles as a photosensitizer when activated by radiation and suggests that these Cu-Cy nanoparticles may be good candidates for PDT in deeply seated tumors when combined with X-rays and conjugated to a tumor-targeting molecule. Significance Copper-cysteamine nanoparticles can be activated directly by X-rays to produce singlet oxygen. The use of copper-cysteamine nanoparticles (conjugated with pH-low insertion peptide) can enhance the effects of X-ray–induced photodynamic therapy, to lead to improved tumor treatment in mice. The results of this study demonstrate the potential of copper-cysteamine nanoparticles with deeply penetrating X-rays in the treatment of mammalian cancer to overcome current limitations of low penetration, light-induced photodynamic therapy treatment that can only treat superficial cancers.