Cascade responsive cell membrane biomimetic nanoplatform for synergistic therapy of esophageal cancer

Photodynamic therapy (PDT) continues to face significant challenges, including optimizing photosensitizers, ensuring adequate oxygen supply, and promoting reactive oxygen species (ROS) production, especially within the tumor microenvironment (TME) characterized by low-oxygen and high glucose metabolism. In this study, a cell membrane biomimetic nanoplatform (CM@CHG) had been designed to enable nitric oxide (NO) self-supply and cyclic cascade therapy. The NO-releasing red fluorescence carbon dots (RCDs) were synthesized from neutral red and L-arginine. RCDs was used as photosensitizer and sonosensitizer, combined with glucose oxidase (GOx), and then disguised as esophageal cancer (EC) cell membrane to form CM@CHG, which had good homology targeting properties. In terms of the cascade reaction, GOx decomposed glucose to produce H₂O₂, which not only alleviated tumor hypoxia, but also promoted RCDs to produce NO for gas therapy. MnO₂ was decomposed by high concentration of glutathione (GSH) and treated with Mn²⁺ as a chemodynamic therapy (CDT). At the same time, the fluorescence of RCDs was restored to realize fluorescence imaging. The results of in vitro and in vivo experiments showed that CM@CHG had chemodynamic, photodynamic, sonodynamic, Gas therapy multimodal performance, good biocompatibility, and effectively improved the anti-tumor effect. Transcriptome analysis confirmed that CM@CHG significantly suppressed the expression of both anti-apoptotic and pro-metastatic genes, while significantly up-regulating both pro-apoptotic and anti-metastatic genes. This study provided an innovative and efficient strategy for the diagnosis and treatment of EC, which had potential application in the field of nanomedicine.