Stimulus-Responsive Nanoparticle-Integrated Dissolving Microneedles for Synergetic Chemo-Photothermal Therapy of Superficial Skin Tumors

In this study, a novel type of stimulus-responsive nanoparticle-integrated dissolving microneedle (DMN) is designed and fabricated as transdermal drug delivery systems for synergetic chemo-photothermal therapy of superficial skin tumors. The nanoparticles have a doxorubicin (DOX)-loaded poly(N-isopropylacrylamide-co-acrylic acid) (PNA) nanogel core and a DOX-loaded polydopamine (PDA) outer layer (PNA–DOX@PDA–DOX), in which PNA provides dual temperature-/pH-responsive property and PDA provides the photothermal effect. Taking hyaluronic acid (HA) with good water solubility and biocompatibility as the material for DMNs, PNA–DOX@PDA–DOX nanoparticle-integrated DMNs (PNA–DOX@PDA–DOX@DMNs) are fabricated. The PNA–DOX@PDA–DOX@DMNs show a good biocompatibility and excellent photothermal effect and can sufficiently penetrate the stratum corneum, rapidly dissolve, and release the drug-loaded nanoparticles into the skin. The drug release rate of PNA–DOX@PDA–DOX@DMNs can be controlled by near-infrared (NIR) laser irradiation, and the release mechanism mainly follows Fickian diffusion. The nanoparticles loaded in DMNs can be rapidly phagocytized by B16F10 cells and release drugs in acidic environments of tumor cells with NIR laser irradiation. The chemo-photothermal therapeutic efficacy of PNA–DOX@PDA–DOX@DMNs is better than the single chemotherapeutic efficacy. The proposed composite DMNs in this study provide a novel transdermal drug delivery strategy for synergetic chemo-photothermal therapy of superficial skin tumors.