Engineering Hyaluronic Acid Microneedles Loaded with Mn2+ and Temozolomide for Topical Precision Therapy of Melanoma

Abstract Topical therapy has received worldwide attention for in situ tumors owing to its higher efficacy of drug delivery. Herein, this work reports a dissolvable multifunctional hyaluronic acid microneedles (HMNs) patch coloaded with temozolomide (TMZ) and MnCl 2 (TMZ/MnCl 2 @HMN) for chemoimmunotherapy of melanoma. HMNs can ensure the stability of TMZ over time, and exhibit fewer side effects with a localized release way. In particular, TMZ not only promotes dendritic cell maturation by triggering immunogenic cell death in tumor cells, but also induces DNA damage that can further enhance the Mn 2+ ‐activated cGAS‐STING (stimulator of interferon genes pathway). As a result, the TMZ/MnCl 2 @HMN multifunctional platform significantly inhibits lung metastases for melanoma, providing a practical strategy for precision therapy of melanoma.