Intelligent Ti3C2–Pt heterojunction with oxygen self-supply for augmented chemo-sonodynamic/immune tumor therapy

Sonodynamic therapy (SDT) is an intriguing approach for killing tumor cells due to its deeper penetration depth compare to photodynamic therapy. However, the therapeutic efficacy of SDT is usually limited by tumor hypoxia and the sonosensitizers' inefficient ability to produce reactive oxygen species (ROS). Herein, we fabricated a novel two-dimensional Ti3C2-based heterojunction nano-sonosensitizer (mTi3C2–Pt) which deposited with noble metal Pt on its surface and then camouflaged with mature dendritic cell (DC) membrane. The deposited Pt can not only improve the SDT and chemodynamic therapy (CDT) effects of Ti3C2 nanosheets due to their enhanced electron capture and oxygen (O2) adsorption ability, but also can break down the endogenous hydrogen peroxide (H2O2) into O2 to moderate tumor hypoxia and relieve the immunosuppressive tumor microenvironment. Moreover, the tumor associated antigens, released as a result of the ROS-induced immunogenic cell death (ICD) after mTi3C2–Pt/R837 treatment, can improve the antitumor immune responses by promoting the DC maturation with the assistance of Toll-like receptor 7 agonist (Imiquimod, R837) and mature DC membrane. The high SDT/CDT and immunotherapy synergistic efficacy of mTi3C2–Pt/R837 is suggested by both in vivo and in vitro assays. Overall, this research offers an exemplification for developing novel Ti3C2-based nano-sonosensitizer for cancer therapy.