Tumor Microenvironment-Directed Multisensitive Nanorobotics for Synergistic Photothermal Therapy/Chemotherapy.

It is of great significance to design a multifunctional nanotherapeutic agent with flexible and intelligent response performance for a tumor microenvironment. Herein, hollow-structured hCu 2- x S@Au derivatives were synthesized for multiswitchable drug release and synergistic photothermal therapy/chemotherapy. The remarkably improved release ratio (over 90%) under higher glutathione concentration and lower pH conditions could be ascribed to the fracture of the disulfide bond and the reduction of force between the drug and nanovehicles. In addition, the shrinking of tetradecanol molecules anchored on the surface of hCu 2- x S@Au by near-infrared (NIR) photo-activation could also enhance the release of drugs in the cavity of hCu 2- x S@Au. After decorating with Au nanoparticles, the favorable electron transitions endowed hCu 2- x S@Au nanoparticles with a high photothermal conversion efficiency, which reaches 36.4% under a NIR laser irradiation of 808 nm. Compared to conventional single/double stimuli-responsive delivery, the proposed multimodal release pattern powerfully overcomes the limitation of insufficient dose as a single/double release unit for a tumor microenvironment was unable to meet the release requirements. After phagocytosis by tumor cells, the continuous release of anticancer drugs facilitated a substantial improvement in the antitumor therapy efficacy by combining chemo- and photothermal therapy in vivo. This design platform can provide a promising strategy for continuous and synergistic tumor therapy.