Polysaccharide-based dissolving microneedles reinforced by metal-polyphenol network: dual-enhancement of mechanical strength and photothermal-triggered drug penetration.

Skin diseases affect approximately 30%-70% of the global population and significantly reduce quality of life. Although polysaccharide-based dissolving microneedles (DMNs) are a minimally invasive transdermal delivery platform with strong clinical potential, their loose molecular packing and weak intermolecular interactions often lead to insufficient mechanical strength, increasing the risk of bending or fracture during insertion into pathological skin. In this study, a metal-polyphenol network (MPN)-mediated dual-enhancement strategy was developed by incorporating an EGCG-iron ion self-assembled precursor into a hyaluronic acid (HA) matrix to generate the preferred MPN-enhanced DMNs (PMN). MPN incorporation regulated the molecular organization of the HA polysaccharide matrix through synergistic hydrogen bonding and metal-ligand coordination interactions, leading to enhanced structural integrity and mechanical robustness. Under 808 nm near-infrared irradiation (NIR), PMN generated localized photothermal heating that disrupted dense tissue barriers and promoted molecular transport, resulting in a 2.67-fold increase in transdermal drug penetration compared with conventional DMNs. In melanoma-bearing mice model, PMN combined with NIR irradiation achieves an 83.5% tumor inhibition rate in a B16 melanoma model with good biosafety. Overall, this work provides mechanistic insights into the structure-property relationship of MPN-regulated polysaccharide matrix and offers a versatile strategy for constructing mechanically robust and multifunctional polysaccharide-based transdermal delivery systems.