Transdermal delivery of Cu-doped polydopamine using microneedles for photothermal and chemodynamic synergistic therapy against skin melanoma

Multimodal nanoformulations with limited side-effects for tumor theranostics that catalyze a cascade of intra-cellular reactions show great potentials for tumor treatment with high specificity and efficiency. In this study, Cu-doped polydopamine nanoparticles (Cu-PDA NPs) have been prepared and embedded into microneedles (MNs) for photothermal and chemodynamic synergistic therapy against skin melanoma, by virtue of enhanced drug transdermal delivery owing to the unique core-shell structure of MNs. This multimodal tumor therapeutic strategy accumulates the high photothermal effect of Cu-PDA NPs (similar to 50.40%) to acquire the energy from NIR irradiation and convert it into heat, and good Fenton-like catalytic activity of Cu+ ions to produce toxic free hydroxyl groups (center dot OH) by reaction with excessive H2O2 in tumor cells, leading to the generation of a new minimally invasive synergistic therapy. The B16F10 mouse melanoma model demonstrates that the active delivery of Cu-PDA NPs results in greatly inhibit proliferation of tumor and induce mixed necrosis/apoptosis of tumor cells in vivo. This study offers a new avenue for the development of microneedles-based microdevices for skin melanoma by a minimally invasive delivery of multimodal nanoformulation.