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Tumor microenvironment-activated Nb2C quantum dots/lactate oxidase nanocatalyst mediates lactate consumption and macrophage repolarization for enhanced chemodynamic therapy.

Abstract
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.
AuthorsYaqian Zhang, Meiting Li, Xiaoge Zhang, Peng Zhang, Zhuoyin Liu, Miao Feng, Guangli Ren, Jie Liu
JournalColloids and surfaces. B, Biointerfaces (Colloids Surf B Biointerfaces) Vol. 221 Pg. 113005 (Jan 2023) ISSN: 1873-4367 [Electronic] Netherlands
PMID36375291 (Publication Type: Journal Article)
CopyrightCopyright © 2022 Elsevier B.V. All rights reserved.
Chemical References
  • Lactic Acid
  • lactate 2-monooxygenase
  • Hydrogen Peroxide
  • Niobium
Topics
  • Lactic Acid
  • Tumor Microenvironment
  • Quantum Dots
  • Hydrogen Peroxide
  • Prospective Studies
  • Niobium
  • Macrophages

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