Photo-Enhanced Chemotherapy with NIR-Triggered Co-Delivery of IR820-MnO2 and Quercetin from Targeted Thermosensitive Liposomes for Photo-Chemo Combination Cancer Therapy

Abstract

We encapsulate versatile photosensitizer (PS) IR-MnO₂, prepared by binding a photothermal agent/PS IR820 to bovine serum albumin-MnO₂ (BSA-MnO₂), in the core of thermosensitive liposomes. The IR-MnO₂ can enhance the efficacy of photodynamic therapy induced by near-infrared (NIR) light by generating oxygen in the acidic tumor microenvironment. Quercetin (Q) was coencapsulated in lipid bilayers to prepare IRQL, which can release IR-MnO₂ and quercetin in response to NIR light. Quercetin can enhance the efficacy of photothermal therapy by sensitizing cancer cells to thermal stress from heat shock protein 70 (HSP70) downregulation, which simultaneously serves as an anticancer agent for chemotherapy. The loading efficiencies of IR-MnO₂ and quercetin in the ∼160 nm IRQL are 83.1% and 65.5%, respectively. For targeted cancer therapy, a cell-penetrating peptide (CPP) was conjugated to IRQL to produce IRQL/CPP with an ∼180 nm size. In vitro studies show enhanced intracellular uptake of IRQL/CPP by U87 glioblastoma cells, which provides a photoenhanced nanoplatform for photochemo combination cancer therapy. Intravenous delivery of IRQL/CPP plus NIR laser irradiation to tumor-bearing nude mice using subcutaneously implanted U87 cells can significantly prevent tumor growth from bioluminescence intensity and tumor volume measurements and extend the animal survival time without biological side effects.

Keywords: IR820; MnO2; heat shock protein; hypoxia; phototherapy; quercetin; thermosensitive liposomes.