A responsive microneedle system for efficient anti-melanoma by combining self-enhanced chemodynamic therapy with photothermal therapy

Abstract Traditional therapies for melanoma suffer from many restrictions, that calls for the development of new treatments with high effectiveness and safety. Recently, employing transdermal microneedle (MN) systems for delivering therapeutic agents has obtained increasing interest as the efficient, minimally invasive, painless, and safe natures. Designing an “all-in-one” multifunctional MN system without complicated integration that can realize enhanced tumor therapy has presented huge promising for clinical application but is still a challenging strategy. Herein, a simple responsive MN system is developed for efficient anti-melanoma by combining self-enhanced chemodynamic therapy (CDT) and photothermal therapy (PTT). This MN system, constructed by biocompatible poly(vinylpyrrolidone) (PVP) as substrate and PVP-stabilized CuO2 nanoparticles (CuO2 NPs) as therapeutic agent, shows good skin-insertion capability and dissolving property that benefit in penetrating skin efficiently to deliver the therapeutic CuO2 NPs into melanoma site. The released CuO2 NPs from MN system can not only produce copper ion (Cu2+) and hydrogen peroxide (H2O2) in response to the acidic environment for catalytic hydroxyl radical (•OH) generation and thus achieve the H2O2 self-supplying CDT, but also can be utilized as a glutathione (GSH)-scavenging agent for further enhancing CDT. Moreover, owing to the loading of CuO2 NPs, such MN system exhibit excellent near-infrared (NIR) photothermal property that can induce local hyperthermia at the melanoma area for PTT. In result, the designed MN system realizes the efficient tumor inhibition with minimal side effects in vivo by the combination therapy, offering a safe and effective melanoma treatment option for patients.