In-Situ-Bloomed Micrometer-Scale Ultrathin Nanosheets\nin Tumor-Microenvironment for\nIntensive Photothermal-Enhanced Chemodynamic Therapy

Abstract

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