Peptide nanoarchitectonics of biomimetic nanozyme synergistically inhibits smooth muscle cell proliferation and promotes endothelial repair to reduce poststenting complications.

Drug-eluting stents are effective for treating cardiovascular disease (CVD), but the procedure can cause mechanical damage to the endothelium, and the released antiproliferative agents delay reendothelialization and impair barrier function, ultimately leading to in-stent restenosis and disruption of vascular homeostasis. Current poststenting therapies, aimed at reducing proliferation and inflammation, often neglect endothelial cell (EC) repair and vascular homeostasis. To address this, we propose the use of a biomimetic nanozyme, HMPB-RAPA@PM&LXW7 (HRPL). Hollow mesoporous Prussian blue (HMPB) nanoparticles serve as carriers for the antiproliferative drug rapamycin (RAPA), which is further modified with a peptide nanoarchitectonics platelet membrane (PM&LXW7). This modification not only targets smooth muscle cells (SMCs) and ECs but also promotes EC repair to accelerate reendothelialization. In response to the acidic inflammatory microenvironment, HRPL releases RAPA to inhibit SMC proliferation and prevent restenosis. Additionally, the nanozyme scavenges reactive oxygen species (ROS), alleviates inflammation, and improves the vascular microenvironment. Both in vivo and in vitro experiments demonstrated that HRPL effectively accelerated reendothelialization, regulated SMC behavior, and reduced inflammation. In conclusion, this peptide nanoarchitectonics biomimetic nanozyme can promote endothelial repair, inhibit neointimal hyperplasia, modulate the inflammatory microenvironment, prevent restenosis, and restore vascular homeostasis, offering a promising approach to reduce complications following clinical stent implantation.