Human Urine–Derived Induced Pluripotent Stem Cell Membranes Enable Personalized Transdermal Nanotherapy for Melanoma

Abstract Melanoma treatment remains limited by drug resistance, immune-related adverse effects, and inadequate tumor-specific drug delivery. Nanoparticle (NP)-based delivery platforms have shown promise, but their clinical translation is hindered by rapid immune clearance and suboptimal biocompatibility. Current membrane-coating strategies often depend on invasive cell sources and lack patient-specific applicability. This study introduces a personalized melanoma therapy platform that integrates MnO2 NPs (MNPs) coated with urine-derived induced pluripotent stem cell (iPSC) membranes into a hydrogel-based transdermal patch. The patient-derived iPSC membrane enhances tumor targeting and immune evasion through the CXCR4/CXCL12 axis, while the MNPs facilitate pH-responsive release of cytotoxic drugs within the tumor microenvironment, maximizing therapeutic efficacy. The hydrogel transdermal patch enables direct, noninvasive delivery to skin lesions, promoting sustained drug exposure and potentially improving patient compliance. By combining autologous cell membrane coating, pH-responsive nanocarriers, and transdermal administration, this platform addresses key limitations of current melanoma therapies and supports the potential for clinical translation of personalized nanomedicine.