Tumor Cell Membrane-Coated Oxygen-Evolving Carbon Nitride Nanozymes Combined with Curcumenol Delivery for Lung Cancer Therapy via 'Open-Source Throttling' Strategy.

Abstract

Although nanozyme-mediated catalytic therapy presents promising prospects for cancer therapy, insufficient tumor targeting, a hypoxic tumor environment and high glutathione (GSH) levels limit its efficacy. Herein, a novel biomimetic Ce-doped carbon nitride nanozyme (MCeCN) with multiclass enzyme catalytic activity, oxygen generation, and targeted delivery of curcumenol (Cur) is developed for the combined treatment of non-small-cell lung cancer (NSCLC). Owing to the wrapping of the A549 cell membrane, these biomimetic nanoparticles demonstrate effective active targeting of NSCLC. Under 808 nm laser irradiation, MCeCNs decompose water at the tumor site to produce oxygen, providing sufficient raw materials for catalytic therapy, and exhibit photothermal effects that facilitate the release of Cur. Within the tumor microenvironment, MCeCNs generate substantial amounts of reactive oxygen species (ROS) via oxidase-like (OXD) and peroxidase-like (POD) catalytic activities. Additionally, MCeCNs can deplete GSH to reduce ROS consumption through glutathione oxidase (GSHOx)-like catalytic activity and convert H₂O₂ into oxygen to increase substrate recycling via catalase (CAT)-like catalytic activity. The biomimetic nanozymes MCeCNs constitute an 'open-source (oxygen production)' and 'throttling (reducing ROS consumption)' strategy to activate cancer cell oxidative stress via the S100A9-mediated Wnt pathway to achieve gas, catalytic and chemotherapeutic combined therapy for NSCLC.