Mild hyperthermia synergized chemotherapy by Bi₂Se₃/MoSe₂ nanosaucers for cancer treatment with negligible thermal resistance

Harsh photothermal temperatures (> 50 ºC) caused heating damage to the normal tissues and induced thermal resistance in cancer cells, which significantly limited the safety and efficacy of photothermal therapy (PTT) in cancer treatment. Mild hyperthermia (< 42 ºC) combined with chemotherapy might solve this issue. Herein, a novel transition metal dichalcogenides nanostructure, namely, Bi₂Se₃/MoSe₂ nanosaucers (BMNSs), was designed to produce mild photo-hyperthermia (mPTT) and combined with chemotherapy to improve the overall antitumor efficacy. The BMNSs were constituted by Bi₂Se₃ hexagonal nanoplates and enclosed with MoSe₂ nanosheets evenly. While the MoSe₂ moiety endowed the nanoplatform with excellent photothermal efficacy, the Bi₂Se₃ substrates provided large specific surface area to anchor more doxorubicin (DOX) molecules as chemotherapeutic agent. Under the stimuli of mPTT/tumor acidic microenvironment, the tumor-specific drug release and the enhanced chemotherapy could be realized, showing impressive therapeutic outcomes against 4T1 cells. The synergetic therapeutic mechanism might be attributed to the mPTT induced cell membrane permeability, and interestingly, the expression of heat shock proteins 70 was not elevated obviously after the synergetic therapy, thus to avoid the tumor thermal resistance and further improve the therapeutic effect. The in vivo anti-tumoral performance of the BMNSs was further studied and complete tumor eradication was achieved without any recurrence and biotoxicity. Not only demonstrating a paradigm of high therapeutic efficacy of mild hyperthermia and synergistic chemotherapy for precise cancer therapy, our findings proved that the cancer therapeutic effect can be improved with minimal side effects through exquisite designing of the microstructures and the physiochemical properties of the nanoplatform.