Photo-Reduction with NIR Light of Nucleus-Targetingt Pt-IV Nanoparticles for Combined Tumor-Targeted Chemotherapy and Photodynamic Immunotherapy

The development of Pt-IV prodrugs which are selectively reduced within cancerous cells into their Pt-II 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 Pt-IV-functionalized nanoparticles that could be excited within the MR region at 808 nm is reported. The polymer backbone which can self-assemble into nanoparticles was functionalized with Pt-IV complexes for chemotherapy, photosensitizers for photodynamic immunotherapy, and nucleus/cancer-targeting peptides. Upon irradiation, the Pt-IV center is reduced to Pt-II and the axially coordinated ligands are released, presenting a multi-modal treatment. While selectively accumulating in tumorous tissue, the nanoparticles demonstrated the ability to eradicate a triple-negative breast cancer tumor inside a mouse model.