Hydrogel-based delivery systems for cutaneous melanoma therapy: from chemical design and crosslinking strategies to structure–activity relationships

Cutaneous melanoma, a malignant neoplasm originating from melanocytes, has exhibited a steadily rising incidence worldwide. Conventional therapeutic strategies often suffer from limited precision, resulting in significant off-target toxicity or failure to prevent disease recurrence. Hydrogels have emerged as a promising platform for localized drug delivery in cutaneous melanoma treatment, owing to their chemically designable three-dimensional networks, tunable crosslinking strategies, and excellent biocompatibility. These structural features enable controlled, on-demand release kinetics and responsiveness to the tumour microenvironment, thereby facilitating multimodal therapy such as chemotherapy, radiotherapy, phototherapy, immunotherapy, and chemodynamic therapy, with enhanced therapeutic efficacy and reduced systemic toxicity. This review systematically examines the chemical composition and crosslinking strategies underpinning hydrogel design, with an emphasis on how these structural parameters influence therapeutic outcomes. Recent advances in tumour microenvironment-responsive hydrogels are further highlighted to elucidate the structure-activity relationships that inform the rational design of next-generation drug delivery systems.