Localized immunotherapy via dissolving microneedles for the prevention of breast cancer recurrence

Breast cancer recurrence post-surgery poses a significant clinical challenge, driven by a paradoxically immunosuppressive wound-healing environment that fosters metastatic relapse. While systemic therapies face dose-limiting toxicities, existing localized platforms like hydrogels and implants lack patient self-administration capabilities. This review evaluates dissolving microneedle (DMN) patches as an innovative, self-administrable, fully bioresorbable transdermal platform for post-surgical immunotherapy. Compared to other microneedle types, DMNs uniquely meet all functional requirements: localized delivery, systemic toxicity mitigation, tunable release, self-administration, and complete resorption. We discussed preclinical advances in biomaterials, cargo design (including STING agonists, TLR7/8 ligands, cytokines, and checkpoint inhibitors), and stimuli-responsive release mechanisms. A novel "kill-reveal-remember" framework is proposed integrating immunogenic cell death, localized checkpoint blockade, and immune memory formation within a single patch. Triple-negative breast cancer (TNBC) is identified as the primary clinical target due to its early recurrence and immunogenicity. However, significant translational hurdles remain. Current preclinical evidence is limited by exclusive use of the murine 4T1 model, short rechallenge intervals, and lack of tissue-resident memory T cells. Furthermore, GMP-compliant manufacturing, sterilization protocols, and stability data are lacking. Successful clinical translation will require advanced humanized models, standardized DMN specifications, and biomarker-driven trials using circulating tumor DNA to fully realize this localized immunotherapeutic approach. Overall, DMN-based localized immunotherapy holds considerable promise for preventing post-surgical breast cancer recurrence by enabling targeted immune modulation with reduced systemic toxicity.