Locoregional Melanoma Therapy by Tissue Adhesive Microneedle Patch-assisted Trans-tumoral Delivery of Anticancer Drug

Melanoma is one of the most threatening cancers due to its metastatic capacity and its incidence is recently increasing due to ozone depletion and excessive exposure to ultraviolet. Adjuvant therapy after primary surgical resection is commonly used to prevent tumor recurrence. However, its clinical outcome is not often satisfactory, mainly due to insufficient local accumulation and the systemic toxicity of antitumor drugs. Herein, we reported a self-biodegradable tissue adhesive microneedle (MN) patch for localized and sustained delivery of doxorubicin (DOX) via microchannels for melanoma growth inhibition. DOX-loaded MN patches were fabricated by casting bioengineered mussel adhesive protein (MAP) solution containing DOX onto poly (dimethyl siloxane) molds with MN-shaped cavities under backside vacuum. The fabricated MAP-based MN patch enabled effective tissue insertion for fresh and living mice skins as well as firm surface adhesion. Notably, DOX-laden MN (DOX-MN) patch significantly suppressed B16F10 melanoma cell proliferation in vitro, while drug-free MN patch did not show any cytotoxicity for both NIH3T3 fibroblasts and B16F10 melanoma cells. In a melanoma-bearing mice model, DOX-MN patch treatment induced greater antitumor efficacy as demonstrated by significant decrease in tumor volume and weight and larger necrotic region compared with intratumoral injection of free DOX. We expect that this strategy can also integrate with other immunomodulators to provide further combinative therapy for effectively eradicating tumors.