Photothermal-promoted calcium influx-regulated phenotypic transformation of VSMCs and free radical scavenging-mediated endothelialization repair for the prevention of in-stent restenosis

• The vascular stent could be coated by PDA-Au nanostructure and then complexed with Ca 2+ , resulting in the photo-thermal conversion capability and the Ca 2+ release capacity of stent. • The present of PDA in the stent could effectively eliminate superfluous reactive oxygen species in the environment to promote the endothelialization repair. • Photothermal, together with the released Ca 2+ , could promote the phenotypic transformation of vascular smooth muscle cells from synthetic phenotype to contractile phenotype, realizing the prevention of in-stent restenosis. Vascular stent implantation is the most direct and effective approach for the treatment of atherosclerosis-related cardiovascular diseases. However, although various stents with the specific features are developed, the in-stent restenosis (ISR) still significantly impacts long-term prognosis of patients and imposes a substantial medical burden. Herein, we coated the bare metal stent (BMS) with polydopamine-Au (PDA-Au) nano-composite and then complexed with Ca 2+ , obtaining BMS@PDA-Au/Ca stent for the prevention of ISR after implantation. Under 808-nm laser irradiation, BMS@PDA-Au/Ca stent increased the temperature around it, further inducing the up-expression of transient receptor potential vanilloid subfamily 1 (TRPV1) of vascular smooth muscle cells (VSMCs). Moreover, BMS@PDA-Au/Ca stent could release Ca 2+ and Ca 2+ was promoted to enter into VSMCs through TRPV1, resulting in the enhanced contractile phenotype and decreased synthetic phenotype of VSMCs. Additionally, PDA with free radical scavenging capacity could accelerate the endothelialization repair. In this way, ISR caused by implantation of stent into the carotid arteries of rabbits could be effectively prevented by using BMS@PDA-Au/Ca stent and laser irradiation. Therefore, this study constructed a novel stent and explored its effect on prevention of ISR, providing an innovative strategy for optimizing the stent implantation treatment of atherosclerotic diseases.