Tumor microenvironment-activated Nb₂C quantum dots/lactate oxidase nanocatalyst mediates lactate consumption and...

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 H₂O₂. Herein, to explore highly efficient CDT agents as well as increase the H₂O₂ content at tumor sites to enhance the efficiency of CDT, a red blood cell (RBC) membrane encapsulated Nb₂C quantum dots/lactate oxidase (LOD) nanocatalyst (Nb₂C QDs/LOD@RBC) was proposed. Nb₂C 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 Nb₂C 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 Nb₂C QDs/LOD@RBC nanocatalyst could efficiently convert the endogenous H₂O₂ into ·OH, while the overexpressed lactate could be catalyzed into H₂O₂ by LOD to replenish the depletion of H₂O₂. The cascaded reaction between Nb₂C quantum dots and LOD eventually enhanced the CDT effect of Nb₂C QDs/LOD@RBC nanocatalyst for tumors growth inhibition. Moreover, the consumption of lactate at tumor sites induced by Nb₂C 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 Nb₂C QDs/LOD@RBC nanocatalyst provides a promising paradigm for tumor inhibition via catalytic cascaded reaction between Nb₂C quantum dots and LOD.