Injectable multi-responsive micelle/nanocomposite hybrid hydrogel for bioenzyme and photothermal augmented chemodynamic therapy of skin cancer and bacterial infection

Activatable theranostic strategy with high specificity and sensitivity for simultaneous skin cancer therapy and anti-infection remains a major challenge. Here, we developed an injectable multi-responsive micelle/nanocomposite hybrid hydrogel (CFMG) for bioenzyme and photothermal augmented chemodynamic therapy (CDT) of both skin tumor and bacterial invasion. The multifunctional hybrid hydrogel was successfully fabricated through incorporating MoS₂@MnFe₂O₄ nanocomposites into a dynamic Schiff-based chemical cross-linked hydrogel of chitosan-grafted-dihydrocaffeic acid (CS-DA) and aldehyde Pluronic F127 (F127-CHO) micelles loaded with glucose oxidase (GOx). The sustained release of GOx induced by the pH-responsive biodegradation of the hybrid hydrogel could continuously consume the intratumoral glucose, produce H₂O₂, and increase acidity. In the gradually enhanced acidic environment, the accelerated release of catalytic iron ions from MoS₂@MnFe₂O₄ nanocomposites catalyzed the decomposition of H₂O₂ into highly toxic [rad]OH via Fenton-like reaction to induce cell death. Remarkably, by combining with a spatiotemporal controllable photothermal hyperthermia, the CFMG hydrogel exhibited bioenzyme and photothermal synergistically enhanced CDT of skin tumor, and demonstrated an almost complete tumor suppression both in vitro (98.8%) and in vivo (97.6%). Moreover, due to the cationic chitosan and the augmented production of [rad]OH, the CFMG hydrogel also demonstrated an effective bacterial eradication (≥99%) both in vitro and in vivo. Taken together, the CFMG hydrogel indicated a great potential for simultaneous skin cancer treatment and antibacterial infection.