Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, China.
MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China.
Biomater Sci. 2022 Nov 8;10(22):6354-6364. doi: 10.1039/d2bm01041k.
Restenosis induced by neointimal hyperplasia is one of the key reasons limiting the long-term success of cardiovascular interventional therapy. However, it remains a serious challenge to completely overcome restenosis because of the dilemma of simultaneously activating human umbilical vein endothelial cells (HUVECs) and inhibiting human aortic smooth muscle cells (HASMCs). Herein, we developed a targeted nanomedicine encapsulating the liver X receptor (LXR) agonist, T0901317, for differentially regulating the behaviors of HUVECs and HASMCs. The stimulatory effect on HUVEC proliferation/migration and the inhibitory effect on HASMC proliferation/migration were confirmed , respectively. In the co-culture system, the competitiveness of HUVECs over HASMCs was notably improved after being treated with T0901317-loaded liposomes. Compared to free T0901317 and non-targeted liposomes, the type IV collagen (Col-IV) targeted liposomes could accumulate in the vascular injured area more effectively and inhibit neointimal hyperplasia in a balloon-induced rat carotid artery injury model. Therefore, targeted delivery of LXR agonist might be a very promising therapeutic strategy for anti-restenosis therapy.
由内膜增生引起的再狭窄是限制心血管介入治疗长期成功的关键因素之一。然而，由于同时激活人脐静脉内皮细胞（HUVECs）和抑制人主动脉平滑肌细胞（HASMCs）的困境，完全克服再狭窄仍然是一个严峻的挑战。在这里，我们开发了一种靶向纳米药物，将肝 X 受体（LXR）激动剂 T0901317 包裹在内，以差异化调节 HUVECs 和 HASMCs 的行为。分别证实了对 HUVEC 增殖/迁移的刺激作用和对 HASMC 增殖/迁移的抑制作用。在共培养系统中，用载有 T0901317 的脂质体处理后，HUVECs 对 HASMCs 的竞争能力明显提高。与游离 T0901317 和非靶向脂质体相比，IV 型胶原（Col-IV）靶向脂质体能够更有效地在血管损伤部位积聚，并抑制球囊诱导的大鼠颈动脉损伤模型中的内膜增生。因此，LXR 激动剂的靶向递送可能是一种很有前途的抗再狭窄治疗的治疗策略。
