Abstract: Melanoma, the most lethal form of skin cancer, is characterized by its highly aggressive and metastatic nature. Postoperative complications following melanoma resection often include elevated tumor recurrence rates, full-thickness skin defects, and bacterial infections. Consequently, preventing tumor recurrence and promoting skin wound healing are crucial considerations after tumor resection. This study developed hyaluronic acid-coated quercetin nanoparticles (HBQ NPs) modified with phenylboric acid, which has good stability under physiological conditions, pH response in acidic environments, and selectivity for A375 cells with CD44 receptor overexpression. A multifunctional microneedle (GHCQ) based on methacrylated gelatin (GelMA), methacrylated hyaluronic acid (HAMA), and carboxymethyl chitosan (CMCS) was prepared and functionalized by quercetin nanoparticles, endowing it with multiple functions such as antitumor, antioxidation, and antibacterial properties. In vitro release studies showed that GHCQ achieved sustained release of 61.96 ± 1.33% quercetin within 21 days in a pH 5.0 environment, demonstrating its pH-responsive drug delivery ability. In vitro antitumor assays over 14 days demonstrated that GHCQ achieved an 83.27 ± 2.08% inhibition rate against melanoma cells (A375). Additionally, GHCQ exhibited robust reactive oxygen species (ROS) scavenging capacity, excellent biocompatibility, and significant antimicrobial efficacy. Animal experiments revealed that GHCQ effectively prevented tumor recurrence while promoting angiogenesis, mitigating inflammation, and accelerating cutaneous regeneration during melanoma treatment in mice. Collectively, this multifunctional microneedle system demonstrates substantial potential for localized tumor wound therapy.
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