Mitochondria-targeting nanomedicines with autophagy inhibitor to enhance cancer photothermal-chemotherapy

Abstract In this article, we fabricated nanomedicines with mitochondrial targeting function and autophagy inhibitor for enhancing cancer photothermal-chemotherapy. The nanoparticles were fabricated with gold nanoparticles (AuNPs) as cores and amphiphilic dextran with (3-carboxypropyl) triphenyl phosphorus bromide and β-cyclodextrin (β-CD) modification (TPP-DCD) as shells; the chemotherapeutic doxorubicin (DOX) and autophagy inhibitor chloroquine (CQ) were encapsulated in the nanoparticles. The TPP-DCD was synthesized via the immobilization of 2-aminoethanethiol modified β-CD and (3-carboxypropyl) triphenylphosphonium bromide on dextran to receive coordination interaction with AuNPs and mitochondria targeting. The size, morphology and properties of the Au@DOX/CQ@TPP-DCD nanoparticles were studied. The nanomedicines efficiently targeted cellular mitochondria to produce reactive oxygen species and photothermal effect under NIR irradiation. The released DOX and CQ could not only kill tumor cells directly, but also inhibit the autophagy of cancer cells to enhance therapeutic effects. Both in vitro and in vivo anticancer activities of the nanomedicines were investigated in detail. The in vivo imaging demonstrated that the Au@DOX/CQ@TPP-DCD nanomedicines exhibited efficient targeting, accumulation and retention in tumor-bearing mice. The apoptosis of cancer cells and tumor suppression were greatly accelerated with the addition of 808 nm NIR irradiation. The Au@DOX/CQ@TPP-DCD nanomedicine exhibited significant synergistic therapy, as 75% of tumors in mice disappeared. The Au@DOX/CQ@TPP-DCD nanoparticle is a promising nanomedicine for cancer therapy with synergistic effects.