Tumor microenvironment-activated NbC quantum dots/lactate oxidase nanocatalyst mediates lactate consumption and macrophage repolarization for enhanced chemodynamic therapy.

Chemodynamic therapy (CDT), which takes advantages of CDT agents to selectively induce tumor cells apoptosis via Fenton or Fenton-like reactions, is considered to have great potential for tumor-specific treatment. However, the therapeutic outcome of CDT still faces the challenges of the lack of efficient CDT agents and insufficient supply of endogenous HO. Herein, to explore highly efficient CDT agents as well as increase the HO content at tumor sites to enhance the efficiency of CDT, a red blood cell (RBC) membrane encapsulated NbC quantum dots/lactate oxidase (LOD) nanocatalyst (NbC QDs/LOD@RBC) was proposed. NbC quantum dots are quite prospective as efficient CDT agents in CDT application due to the intrinsic merits such as abundant active catalytic sites, satisfactory hydrophilicity, and good biocompatibility. The encapsulation of NbC QDs and LOD into RBC membrane was to prolong the in vivo circulation time of the nanocatalyst and increase its tumor sites accumulation. The accumulated NbC QDs/LOD@RBC nanocatalyst could efficiently convert the endogenous HO into ·OH, while the overexpressed lactate could be catalyzed into HO by LOD to replenish the depletion of HO. The cascaded reaction between NbC quantum dots and LOD eventually enhanced the CDT effect of NbC QDs/LOD@RBC nanocatalyst for tumors growth inhibition. Moreover, the consumption of lactate at tumor sites induced by NbC QDs/LOD@RBC nanocatalyst leads to the increased infiltration of antitumoral M1 tumor-associated macrophages, which alleviated the immunosuppression of the tumor microenvironment and further maximized the therapeutic outcome of CDT. Taken together, the NbC QDs/LOD@RBC nanocatalyst provides a promising paradigm for tumor inhibition via catalytic cascaded reaction between NbC quantum dots and LOD.