Nanoparticle-loaded microneedles as advanced transdermal systems for skin cancer management.

Skin cancer remains a major global health burden, with over 330,000 new melanoma cases reported in 2022 and an estimated 1.5 million new skin cancer cases worldwide. Conventional treatment modalities, including surgery, chemotherapy, and radiotherapy, are often associated with systemic toxicity, therapeutic resistance, and cosmetic complications. Recent preclinical studies have demonstrated that microneedle-assisted nanoparticle delivery systems enable efficient transdermal penetration, localized drug deposition, and enhanced antitumor efficacy in both melanoma and non-melanoma skin cancer models. These minimally invasive platforms bypass the stratum corneum and improve local drug bioavailability while minimizing systemic side effects. Established nanocarriers, including liposomes, polymeric, metallic, and hybrid nanoparticles, have been successfully incorporated into dissolving and biodegradable microneedle arrays, enabling sustained and stimuli-responsive release of chemotherapeutic, phototherapeutic, and immunotherapeutic agents. However, existing evidence is largely limited to in vitro and small-animal studies, and critical gaps remain regarding long-term safety, repeated-dose skin tolerability, large-scale manufacturing reproducibility, and clinical translation. Further investigations are required to optimize microneedle geometry, nanoparticle loading capacity, dose uniformity, and regulatory-compliant fabrication strategies, as well as to establish robust clinical efficacy through well-designed human trials. Overall, microneedle-assisted nanoparticle hybrid systems represent a promising next-generation transdermal platform for skin cancer management, with substantial preclinical validation but a clear need for translational and clinical studies to enable routine clinical application.