血小板膜包被仿生纳米前药用于高效靶向抑制血管再狭窄的研究

Improving the therapeutic target and controlled drug release properties of nano-drug, are the key factors to enhance drug therapeutic efficiency and safety. However, because of the difficultly constructed complex surface, it is extremely hard for nano-carriers to be recognized and approved by organism, and subsequently be phagocytized by immune system as foreign matter failing to deliver drug to therapeutic site. The biomimetic platelet strategy can provide the target ability of drug delivery to wound vessel. Thus, this project proposes to construct the stimuli-responsive nano-prodrug, and further fabricate the biomimetic nano-prodrug by platelet cloaking. The biomimetic nano-prodrug retaining the target function of platelet, can evade the immune system and targetly deliver to the vascular wound. In addition, target aggregated biomimetic nano-prodrug can control drug release and reduce the systemic side-effect. The innovation of this project proposal is to coordinate the strategy of platelet cloaked biomimetic nano-drug and prodrug design, shield the immune response, efficiently deliver and retain drug to the targeted vascular wound, show sustained and controlled drug release profile for vascular restenosis inhibition, facilitate the vascular wound efficient and safe healing. Thus, the study achievement would be important for scientific research and clinical application in intelligent drug delivery and tissue engineer repair.

改善纳米药物病灶部位靶向性及可控药物释放是提高药物治疗效用及安全性的关键。然而，由于复杂的外表面难以构建，纳米药物载体很难被正常的生物交互认可，导致其被作为异物被免疫细胞吞噬而难以靶向输送药物到病灶部位。利用仿生血小板设计策略能够提供受损血管药物递送靶向性。因此，本项目拟构建刺激响应纳米前药，并通过进一步血小板膜包被制备具有仿生功能的纳米前药。仿生纳米前药表面保留了血小板靶向功能，能够躲避免疫系统的追捕，靶向递送药物到受损血管。此外，靶向聚集的仿生纳米前药能够实现可控药物释放并降低药物全身毒副作用。本项目的创新点在于：协同血小板膜包被的仿生纳米药物及前药设计，屏蔽免疫系统的响应，高效靶向纳米药物递送及滞留血管受损部位，实现持续性可控药物释放，从而防治损伤血管愈合过程中血管再狭窄发生，促进受损血管高效、安全愈合。该研究成果将对智能药物递送、组织工程修复具有重要的科学研究意义及临床应用价值。

心血管疾病发病率及致死率在全球范围内均位列第一，是严重威胁人类健康的首要疾病。在项目的支持下，为了改善传统纳米药物“非己”特性导致的药物治疗效用性及安全性不佳的问题，本研究结合血管病理高效、靶向药物递送及可控药物释放两个关键因素，本项目关键点在于协同血小板膜基仿生纳米药物及前药设计，屏蔽免疫系统的响应，高效、靶向纳米药物递送及滞留于血管病理部位，实现持续性可控药物释放。研究结果明确了血小板膜基仿生纳米粒子对血管损伤部位的靶向性，具有逃避巨噬系统清除及高效靶向性功能。同时，表面前药改性实现了协同前药设计策略，响应微酸环境（pH < 6.5）完成了长效、可控药物释放，充分提高药物的生物利用度及治疗效用，显著降低药物毒副作用。该研究构建高效血管损伤靶向修复的仿生纳米药物，实现药物治疗的高效性及安全性，对推动仿生医用纳米药物在智能纳米药物及组织修复功能材料的进一步发展提供了新的解决思路。