"In situ endothelial modulation and transduction" strategy driven by biomimetic H₂S delivery system for targeted repair of vascular injury.

Abstract

Vascular recanalization mediated by the interventional therapy can reduce cardio-cerebrovascular disease burden. However, its long-term outcomes are often undesired owing to (1) inevitable mechanical damage to the vasculature that triggers pathological remodeling, presented as local inflammation/oxidative stress, intimal hyperplasia, and delayed endothelial healing; and (2) long-term and frequent use of antiplatelet drugs, which increase bleeding risks. These challenges highlight the necessity for rapid vascular repair and minimizing dosing frequency, which are currently unmet due to the lack of a highly efficient delivery/therapy strategy. Herein, we formulated a damaged vascular endothelial-targeted hydrogen sulfide (H₂S) nanomedicine, utilizing the endothelial cells (ECs) as a delivery destination rather than the traditional smooth muscle cells (SMCs) for overcoming drug delivery barriers. This drug targets the ECs, where it releases H₂S in a sustained manner to promote endothelial regeneration and in situ transduce signaling from ECs for suppressing SMC-mediated intimal hyperplasia and reprogramming Mφ to inhibit local inflammation. A single dose of therapy achieved satisfactory vascular repair and safety within 28 days in the carotid artery injury model. This study provides a novel solution for vascular repair and advances the development of a drug delivery approach.