Mokhles, FatemehGonzález Valdivieso, JuanMoosavi, Mohammad AminCordani, Marco2025-10-212025-10-212025-06Mokhles F, Gonzalez-Valdivieso J, Moosavi MA, Cordani M. Advances in nanoparticle-mediated transdermal delivery of nucleic acids as therapy of skin disorders and cancer. Current Opinion in Biomedical Engineering 2025;35:100611. https://doi.org/10.1016/j.cobme.2025.100611.10.1016/j.cobme.2025.100611https://hdl.handle.net/20.500.14352/125218Funding J.G-V acknowledges the funding from the European Union - NextGenerationEU program. MC was supported by grant RYC2021-031003I funded by MICIU/AEI/10.13039/501100011033 and by European Union NextGenerationEU/PRTR.Transdermal delivery of gene and RNA therapies represents a promising strategy in addressing genetic skin disorders and cancers, offering localized treatment with enhanced bioavailability and reduced systemic side effects. Despite these advantages, the stratum corneum presents a formidable barrier to the delivery of nucleic acids due to its dense lipid-protein structure and susceptibility to enzymatic degradation. Recent innovations in nanoparticle technologies, such as cationic liposomes and polymer-based carriers, have overcome these challenges by enhancing penetration, stability, and target specificity. Additionally, techniques like microneedles and iontophoretic applications further facilitate effective delivery into skin layers. Advanced formulations combining nanoparticles with therapeutic agents such as siRNA and CRISPR-Cas9 demonstrate significant potential in tumor growth inhibition, immune modulation, and gene correction. These approaches offer targeted therapeutic options, reduce drug resistance, and support genetic modifications for skin conditions. While challenges like immunogenicity and systemic degradation persist, emerging integration of artificial intelligence (AI) optimizes nanoparticle design and delivery systems. AI-driven advancements promise to refine transdermal delivery technologies, advancing precision medicine in dermatological applications and cancer therapy.engAttribution-NonCommercial 4.0 Internationalhttp://creativecommons.org/licenses/by-nc/4.0/journal article2468-4511https://doi.org/10.1016/j.cobme.2025.100611https://www.sciencedirect.com/science/article/pii/S2468451125000364open access577.2615.03Biología molecular (Biología)Farmacología (Medicina)Biotecnología2415 Biología Molecular2302.22 Farmacología Molecular3207.13 Oncología