Recent advances in dissolving microneedles for breast cancer immunotherapy: local delivery and tumor microenvironment remodeling

Abstract

Breast cancer is generally characterized by limited immunogenicity. Although immune checkpoint inhibitors (ICIs) provide survival benefits in a subset of patients with triple-negative breast cancer (TNBC), overall response rates remain limited and are accompanied by pronounced therapeutic heterogeneity and systemic immune-related adverse events. The immunosuppressive tumor immune microenvironment (TIME), characterized by restricted antigen presentation, limited effector T-cell infiltration, and enrichment of immunosuppressive cell populations, represents a key barrier to durable immunotherapy benefit. Dissolving microneedles (DMNs) represent a minimally invasive transdermal delivery system that bypasses the stratum corneum barrier. They enable the delivery of antigens and immunomodulatory molecules into the epidermis and superficial dermis enriched in antigen-presenting cells (APCs), thereby facilitating efficient peripheral immune priming while reducing systemic exposure. This review summarizes the material composition and microstructural design of DMNs, their transdermal immunodelivery characteristics, and recent advances in breast cancer immunotherapy. It further highlights the mechanisms by which DMNs mediate peripheral immune activation and remodel the TIME, as well as their potential in combination with other immunotherapeutic strategies. Overall, DMNs represent a promising strategy that may improve the efficacy and safety of breast cancer immunotherapy by enabling localized delivery, efficient peripheral activation, and coordinated microenvironment remodeling.