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

[Display omitted] • Microneedle transdermal drug delivery has the advantages of minimally invasive, safe and efficient. • The core–shell type microneedle is obtained by a vacuuming and hot melting strategy. • The microneedle system is designed to release drugs quickly and improve the utilization rate of drugs. • The photothermal conversion efficiency of Cu-PDA NPs is increased to 50.40%. • Transdermal delivery of Cu-PDA NPs using MNs exhibited PTT-CDT synergistic therapy against skin melanoma. Multimodal nanoformulations with limited side-effects for tumor theranostics that catalyze a cascade of intracellular 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 (~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 (‧OH) by reaction with excessive H 2 O 2 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. [ABSTRACT FROM AUTHOR]