Enhanced Photothermal Therapy of Breast Cancer via Co-Loading With Autophagy Inhibitor

Abstract

\n Photothermal therapy (PTT) usually causes hyperthermia and damages healthy tissues. Developing a PTT platform using mild irradiation, while enhance the theraputical effects attracts increasing attention. Here, this study developed a theranostic poly(D,L-lactic-co-glycolic acid) (PLGA) nanoplatform loaded with a near-infrared (NIR) dye (new indocyanine Green IR820), autophagy inhibitor (chloroquine, CQ) and a fluorescence imaging agent (ZnCdSe/ZnS quantum dot, QD) by the double emulsion solvent evaporation technique (W1/O/W2). The resulting hybrid PLGA nanoparticles with IR820/ZnCdSe/ZnS/CQ co-loading (termed PIFC NPs) approximated 240 nm in diameter and had excellent monodispersity, fluorescence and size stability, and biocompatibility. PIFC NPs displayed photothermal effects, and the released CQ remarkably decreased autolysosome degeneration by lysosomes in cancer cells, thereby enhancing the suppressive effect on autophagy as well as resistance to photothermia. Anticancer effects were enhanced both in cellular and animal experiments attributed to the combined effects exerted by PIFC NPs and mild NIR irradiation. Moreover, PIFC NPs significantly accumulated in tumors because of enhanced permeability and retention (EPR) effect, enabling high-spatial resolution, real-time fluorescence imaging of solid tumors. The present study developed a novel PTT platform showing potentially enhanced therapeutic efficacy.