Abstract
Skin cancer, particularly malignant melanoma, is one of the most prevalent cancers globally, affecting millions annually. Traditional treatments like excision, chemotherapy, and immunotherapy often fail due to their invasiveness, toxicity, and poor drug delivery efficiency caused by skin barriers. Microneedles (MNs) offer a minimally invasive alternative, directly penetrating the skin to deliver drugs to tumor sites while minimizing side effects. However, their penetration depth is limited, and they do not address metastatic lesions. This study developed a gas motor-driven multi-responsive microneedle patch that significantly enhances subcutaneous drug penetration through a gas propulsion mechanism, greatly expanding the drug's diffusion range. Combined with photothermal therapy (PTT) and chemotherapy, this approach rapidly kills melanoma cells locally, induces immunogenic cell death (ICD), and uses anti-PD-1 antibodies (aPD-1) targeting immune checkpoints to enhance efficacy, overcome tumor immune escape, and activate systemic immune responses, achieving remote tumor suppression through local treatment only.