Smart near-infrared manganese-doped carbon dot-microneedle assemblies for tumor microenvironment-activated photodynamic-chemodynamic combined therapy

Photodynamic therapy (PDT) that utilizes photosensitizers to induce reactive oxygen species (ROS) generation has become an important option in cancer clinical treatment due to its spatiotemporal controllability and non-invasive treatment characteristics. However, the inherent characteristics of the tumor microenvironment limit oxidative stress. In addition, traditional photosensitizers have problems such as poor water solubility, poor photostability and complex synthesis, which hinder the clinical application efficacy of PDT. To further enhance the efficacy of PDT, this study constructed a manganese-doped carbon dots (Mn-CDs) nanosystem with a dual-functional synergistic mechanism. It can catalyze endogenous H2O2 to undergo a Fenton-like reaction in response to the weakly acidic microenvironment of tumors, continuously generating ·OH. Under laser irradiation, it can accelerate the Fenton like reaction to produce 1O2 (quantum yield of 0.39), deplete glutathione (GSH) to disrupt the intracellular redox balance, and the apoptosis rate can reach 86.14 %. The tumor-bearing mouse model showed that the tumor growth inhibition rate could reach 95.5 %. Notably, the treatment dose was precisely delivered through hyaluronic acid dissolved microneedles for transdermal delivery, ensuring a local effective drug concentration while reducing systemic toxicity, providing a new solution that is both highly efficient and safe for targeted treatment of oral squamous cell carcinoma.