The fabrication of functional nanoparticles with unique ultra-sensitivity to endogenous tumor microenvironment (TME) is of great significance for their improved theranostic performance and easy excretion out of the body, which has not been realized among diverse nano-sized photothermal agents for photothermal therapy (PTT) of tumor. In this work, we report on the synthesis of 2D ultrathin MnO₂ nanosheets for highly efficient PTT against tumor with ultra-sensitivity to endogenous TME. These ultrathin 2D MnO₂ nanosheets show the intriguing characteristic of disintegration and releasing of Mn²⁺ in response to the mild acidic condition and elevated reducing microenvironment of TME, which has successfully realized the pH- and reducing-responsive T₁-weighted magnetic resonance imaging of tumor. Importantly, the high PTT efficiency of 2D MnO₂ nanosheets responsive to exogenous NIR irradiation have been systematically demonstrated both in vitro and in vivo for suppressing the tumor growth. This first report on the exploring of TME-sensitive photothermal agents with concurrent diagnostic and therapeutic (theranostic) functions significantly broadens the biomedical application of 2D functional biomaterials, which also promotes the further potential clinical translations of nano-sized photothermal agents.

对内源性肿瘤微环境（TME）具有独特的超敏感性的功能性纳米粒子的制备对于其改善的细胞诊断性能和易于从体内排泄具有重要意义，这在用于光热疗法的各种纳米级光热剂中尚未实现（ PTT）。在这项工作中，我们报告了二维的超薄MnO ₂纳米片的合成，该纳米片用于高效PTT对抗肿瘤，并对内源性TME具有超敏感性。这些超薄的二维MnO ₂纳米片表现出耐温和的酸性条件下Mn ²⁺崩解和释放的有趣特征，并提高了TME的还原微环境，从而成功实现了pH响应和还原响应T ₁加权磁共振成像。重要的是，已在体外和体内系统地证明了响应于外源NIR辐射的2D MnO ₂纳米片的高PTT效率可抑制肿瘤的生长。关于具有同时诊断和治疗（热疗）功能的TME敏感光热试剂的探索的第一份报告显着拓宽了2D功能生物材料的生物医学应用，这也促进了纳米级光热试剂的进一步潜在临床翻译。