Photo-Reduction with NIR Light of Nucleus-Targeting PtIV Nanoparticles for Combined Tumor-Targeted Chemotherapy and Photodynamic Immunotherapy.

Abstract

The development of PtIV prodrugs which are selectively reduced within cancerous cells into their PtII therapeutically active species has received increasing attention within the last decade. Despite recent research progress, the majority of investigated compounds are excited using ultraviolet or blue light. As the light penetration depth is low at these wavelengths, the treatment of deep-seated or large tumors is limited. To overcome this limitation, herein, the example of PtIV -functionalized nanoparticles that could be excited within the NIR region at 808 nm is reported. The polymer backbone which can self-assemble into nanoparticles was functionalized with PtIV complexes for chemotherapy, photosensitizers for photodynamic immunotherapy, and nucleus/cancer-targeting peptides. Upon irradiation, the PtIV center is reduced to PtII and the axially coordinated ligands are released, presenting a multimodal treatment. While selectively accumulating in tumorous tissue, the nanoparticles demonstrated the ability to eradicate a triple-negative breast cancer tumor inside a mouse model.