Tumor Microenvironment Responsive Oxygen-Self-Generating Nanoplatform for Dual-Imaging Guided Photodynamic and Photothermal Therapy

Developing a smart nanoplatform for cancer diagnosis and treatment under the hypoxic and acidic tumor microenvironment (TME) remains a great challenge. Herein, a TME responsive Ce6-MnO₂/CNTs (CMCs) nanoplatform with oxygen-self-generation property and enhanced permeability and retention effect (EPR) has been successfully prepared for synergistic photothermal/photodynamic therapy. Carbon nanotubes (CNTs) were uniformly coated with cross-linked MnO₂ flakes, then the obtained MnO₂/CNTs (MCs) were incubated with Chlorin e6 (Ce6) to fabricate CMCs. In the TME, MnO₂ in CMCs (targeted accumulation in tumor site) could react with endogenous H₂O₂ and H⁺ to supply oxygen in situ for Ce6 to produce cytotoxic singlet oxygen (¹O₂), which significantly enhances the photodynamic therapy (PDT) efficiency. Moreover, CNTs could also be utilized as a photothermal agent for both photothermal imaging and therapy (PTT) to further improve the therapeutic efficacy. In addition, the photosensitizer Ce6 could also be used for in vitro and vivo fluorescence imaging. The results demonstrate that the smart tumor microenvironment responsive nanoplatform Ce6-MnO₂/CNTs with EPR effect and oxygen-self-generation property hold great potential in photothermal/fluorescence imaging guided synergistic PDT/PTT for cancer treatment in clinic.