A core–shell structured biphasic microneedle system as an elite squad for combating melanoma with “three-in-one” therapeutic power

Achieving optimal therapeutic outcomes with microneedle (MN) technology requires a high drug payload, tunable mechanical strength, and robust drug stability-key attributes in demand for transdermal drug delivery. This work introduces a core-shell structured biphasic MN system designed to combat melanoma with "three-in-one" therapeutic power. The MN base, made of water-insoluble poly(methyl methacrylate), forms a biphasic interface with the needle body. Acting as a "shield", the base effectively prevents drug migration and enhances the drug-loading capacity of the needle body. The needle body features a core-shell design, with a shell composed of photo-cross-linked hydrogel. This shell serves as a "spear" to optimize mechanical properties of MNs, efficiently piercing the skin barrier. Meanwhile, the core section of MN, constructed from hyaluronic acid, acts as a "bow and arrow" to preserve the bioactivity of chlorin e6 nanoparticles for launching an effective "attack" on melanoma cells through photodynamic therapy. The MN system demonstrates exceptional mechanical performance and enhanced anticancer efficacy against melanoma cells both <i>in vitro</i> and <i>in vivo</i>. In summary, this study introduces a new "elite squad" strategy that integrates three critical functionalities into a single MN platform, offering significant potential for treating melanoma and other malignant skin conditions.