Oxygen and Pt(ll) self-generating conjugate for synergistic photo-chemo therapy of hypoxic tumor

Abstract

Cancer cells in hypoxic tumors are remarkably resistant to photodynamic therapy. Here, we hypothesize that an oxygen and Pt(ll) self-generating multifunctional nanocomposite could reverse the hypoxia-triggered PDT resistance. The nanocomposite contains Pt(IV) and chlorin e6, in which upconversion nanoparticles are loaded to convert 980 nm near-infrared light into 365 nm and 660 nm emissions. Upon accumulation at the tumor site, a 980 nm laser is used to trigger the nanocomposite to generate O-2 for consumption in the PDT process and to produce cytotoxic reactive oxygen species. The composite also releases active Pt(ll) for synergistic photo-chemo therapy to enhance antitumor efficiency. The oxygen and Pt(ll) self-generating prodrug is shown to have high potential to inhibit tumors out of the range of UV light, to overcome the hypoxia-triggered PDT resistance and significantly improve anticancer efficacy by the synergistic PDT-chemotherapy.