Near-infrared light-driven multifunctional metal ion (Cu²⁺)-loaded polydopamine nanomotors for therapeutic angiogenesis in critical limb ischemia

Most of the current nanomedicine-based treatments for critical limb ischemia (CLI) only aim at promoting angiogenesis, ignoring the negative influence on the therapeutic effects caused by the complex pathological micro-environment of ischemic tissue. Herein, near-infrared (NIR) light-driven metal ion (Cu²⁺)-loaded polydopamine (PDA) nanomotors (JMPN@Cu²⁺) is designed and prepared. Due to the good antioxidant and anti-inflammatory activities of PDA, JMPN@Cu²⁺ exhibits excellent biocompatibility and significantly improves the ischemic micro-environment. Additionally, based on superior photothermal conversion effect and jellyfish-like structure, the nanomotors are quickly propelled under NIR laser with low energy intensity to acquire the ability of movement and facilitate intracellular uptake of JMPN@Cu²⁺ by endothelial cells, resulting in the enhanced pro-angiogenic effect of Cu²⁺. Moreover, in vivo experimental findings show that JMPN@Cu²⁺ combined with NIR irradiation can successfully accelerate blood flow recovery and improve muscle repair. Taking these results together, this kind of nanomotor can promote angiogenesis along with ischemic micro-environment amelioration, holding great potential applications for the treatment of limb ischemia.