Tumor microenvironment-activated Nb2C 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 H 2 O 2. Herein, to explore highly efficient CDT agents as well as increase the H 2 O 2 content at tumor sites to enhance the efficiency of CDT, a red blood cell (RBC) membrane encapsulated Nb 2 C quantum dots/lactate oxidase (LOD) nanocatalyst (Nb 2 C QDs/LOD@RBC) was proposed. Nb 2 C 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 Nb 2 C 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 Nb 2 C QDs/LOD@RBC nanocatalyst could efficiently convert the endogenous H 2 O 2 into ·OH, while the overexpressed lactate could be catalyzed into H 2 O 2 by LOD to replenish the depletion of H 2 O 2. The cascaded reaction between Nb 2 C quantum dots and LOD eventually enhanced the CDT effect of Nb 2 C QDs/LOD@RBC nanocatalyst for tumors growth inhibition. Moreover, the consumption of lactate at tumor sites induced by Nb 2 C 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 Nb 2 C QDs/LOD@RBC nanocatalyst provides a promising paradigm for tumor inhibition via catalytic cascaded reaction between Nb 2 C quantum dots and LOD. [Display omitted] • The Nb 2 C QDs/LOD@RBC nanocatalyst has been developed for enhanced CDT. • Enhanced CDT is attribute to the cascaded reaction between Nb 2 C QDs and LOD. • The nanocatalyst consumes lactate to increase the infiltration of M1 macrophages. [ABSTRACT FROM AUTHOR]