Abstract
Microneedles have demonstrated value in targeted treatment of dermatosis. Current investigation aims to enhance the functions and optimize substance delivery to improve therapeutic effects. Here, we present innovative shell-core microneedles with light-pH dual responsiveness for spatiotemporal sequential release of multiple Chinese herb drugs to treat scleroderma. By using a stepwise template-assisted method, we effectively prepare a hydrogel-based core layer containing polydopamine-MXene (P-MXene) loaded with triptolide (TP), and a shell layer composed of polyvinyl alcohol (PVA) encapsulating paeoniflorin (Pae). P-MXene can adsorb the sparingly soluble TP to ensure its encapsulation efficiency and contribute to the synergistic photothermal effect benefitting from its excellent photothermal conversion ability. Besides, PVA can rapidly dissolve upon microneedle piercing into the skin and quickly release the anti-inflammatory and detoxifying Pae, establishing a favorable low-acid subcutaneous environment. In response to pH changes and near-infrared effects, TP is sustainably released from P-MXene and delivered through the swollen pores of the hydrogel. On the basis of these characteristics, we demonstrate that these microneedles could effectively reduce profibrotic key cytokines interleukin-1β and transforming growth factor-β, thereby reducing collagen deposition and decreasing epidermal thickness, ameliorating skin fibrosis and capillary lesion in scleroderma mouse models. These findings highlight the important clinical potential of these microneedles in the treatment of skin diseases.