In-Situ-Bloomed Micrometer-Scale Ultrathin Nanosheets in Tumor-Microenvironment for Intensive Photothermal-Enhanced Chemodynamic Therapy

Chemodynamic therapy (CDT), as the emerging modality of cancer therapy based on Fenton or Fenton-like reactions, still suffers from low efficacy of hydroxyl radical generation, which requires full exposure of reaction sites of CDT nanoagents to intracellular H2O2. However, the amount of exposed reaction sites is severely restrained by the controlled size (<200 nm) and the limited specific surface area of nanoagents. Herein, we highlight the in-situ bloomed micrometer-scale CoMn-based layered double hydroxide (CoMn-LDH) ultrathin nanosheets, which are derived from CoMn boride-based CMB@ss-SF nanospheres in response to overexpressed glutathione (GSH) and dissolved oxygen in tumor microenvironment (TME), accomplishing intensive photothermal-enhanced CDT. The micrometer-scale CoMn-LDH ultrathin nanosheets would provide abundant reactive sites to accelerate heterogeneous Fenton-like reaction as well as GSH depletion, eliciting quick release of metal ions and further realizing intensive homogeneous Fenton-like reactions for center dot OH generation. Moreover, the nanoagent can harvest 808 nm light into heat, which can be utilized to promote the CDT efficacy and realize photoacoustic imaging (PAI). Because of acidity and overexpressed GSH in TME, the nanoagent exhibited superior biodegradability. Benefiting from the synergistic advantages, CMB@ss-SF with negligible cytotoxicity completely eradicated the tumors in mouse. This work provides avenue for developing CDT nanoagents.