Multifunctional Nanocomposite Hydrogel with Enhanced Chemodynamic Therapy and Starvation Therapy for Inhibiting Postoperative Tumor Recurrence

Surgical resection is the primary treatment for melanoma; however, preventing tumor recurrence after resection remains a significant clinical challenge. To address this, we developed a multifunctional nanocomposite hydrogel (H-CPG) composed of glucose oxidase (GOx)-coated CuS@PDA@GOx (CPG) nanoparticles, aminated hyaluronic acid (HA-ADH), and oxidized rhizomatous polysaccharides (OBSP), which are interconnected through hydrogen bonds and dynamic Schiff base linkages. In the acidic tumor micro-environment, the hydrogel releases GOx, catalyzing the production of hydrogen peroxide (H₂O₂), which enhances chemokinetic activity through a Cu²⁺-mediated Fenton-like reaction. This process generates hydroxyl radicals that intensify oxidative stress and promote macrophage polarization from the M2 to M1 phenotype. This polarization triggers the release of pro-inflammatory cytokines, thereby inhibiting tumor recurrence. Additionally, the hydrogel induces photothermal effects that help eradicate residual bacteria at the wound site. Overall, the H-CPG hydrogel offers a dual mechanism to prevent melanoma recurrence and reduce resistance to monotherapy, presenting a promising strategy for postoperative tumor management.