Biomimetic smart mesoporous carbon nanozyme as a dual-GSH depletion agent and O2 generator for enhanced photodynamic therapy

Photodynamic therapy (PDT) has been thriving in the theranostics of cancer in recent years. However, due to a series of problems such as high concentration of GSH and insufficient O2 partial pressure in the tumor micro-environment, it is difficult to achieve the desired therapeutic effects with single PDT. Mesoporous carbon (MC-COOH) has been widely used in photothermal therapy (PTT) due to its high photothermal conversion efficiency and drug loading. In addition, we have discovered that MC-COOH owned high-efficiency glutathione oxidase-like activity for intracellular lasting GSH consumption. Hence, a smart mesoporous carbon nanozyme (CCM) was designed as a dual-GSH depletion agent and O2 generator combined with PTT to overcome the dilemma of PDT. MnO2-doped carbon nanozyme (MC-Mn) was developed as the photothermal vehicles for the efficient loading of photosensitizer (Ce6). Subsequently, 4T1 membrane-coated nanozyme (Ce6/CCM) was constructed to achieve homologous targeting capability. The carbon nanozyme owned the sustained dual-GSH depletion function through MC-COOH and MnO2, which greatly destroyed the antioxidant system of the tumor. Meanwhile, MnO2 could produce affluent O2 in the presence of H2O2, thereby alleviating the hypoxic state of tumor tissues and further promoting the generation of ROS. In addition, the novel carbon nanozyme was designed as photoacoustic imaging (PAI) agent and magnetic resonance imaging (MRI) contrast for real-time imaging during tumor therapy. In summary, this work showed that the biomimetic carbon nanozyme could be used as dual-GSH depletion agent and O2 generator for dual-mode imaging-guided PTT-PDT.