动脉粥样硬化易损斑块早期预警及治疗

Vulnerable plaques have been the focus for the prevention and treatment of cardiovascular events, whose early warning and treatment make a worldwide conundrum in the field of cardiovascular diseases. A vulnerable plaque is not usually associated with severe arterial stenosis. Regular imaging techniques can reveal the extent of vessel stenosis, yet unable to reflect plaque stability thus missing the culprit of adverse cardiovascular events. Despite OCT's capability of identifying vulnerable plaques, its invasiveness, costliness and poor coverage among basic-level hospitals stand out. Nano-carrier can achieve early diagnosis and treatment of vulnerable plaques. We've suceeded, by developing LyP-1-liposome nano-particle, in the targeted diagnosis and treatment of vulnerable plaques. Traditional liposomes, however, lack stability that precludes release of drugs into bloodstream before reaching the target, forfeiting targeting features. A portion of targeted drugs get lost into the bloodstream, bringing about systemic adverse reactions. This project utilized mesoporous silica nanoparticle with nano-gold coupled on their surface and adiponectin, a cellular factor inducing reverse cholesterol transport, lining the lumen. Mesoporous silica nanoparticles were modified with LyP-1 molecules which endowed the nano-carriers with targeting capabilities. All these efforts combine to develop these nano-particles that diagnose and treat with excellent stability, targeting capability and safety, both X-ray imaging opaque and agent-delivering. The implementation of this technique ensures early warning and treatment of vulnerable plaques, guiding the precision therapy of coronary heart diseases.

易损斑块是心血管事件防治焦点，其早期预警与治疗是心血管病领域的世界性难题。易损斑块所导致的血管狭窄程度常常不高，普通影像检查只能显示血管狭窄程度，不能有效反映斑块的稳定性，无法预警心血管事件的真正元凶。虽然OCT可识别易损斑块，但检查有创、价格昂贵、基层医院难以普及。纳米载体可实现易损斑块的早期诊疗。我们已成功研发了LyP-1-脂质体载药纳米微粒，实现了易损斑块靶向诊疗。但是传统脂质体稳定性差，未及靶点已有大量药物释放入血，丧失靶向性。采用药物靶向治疗，仍有部分药物进入全身血液系统，带来全身副反应。本项目利用介孔硅载体，纳米金偶联于载体表面，内腔负载介导胆固醇流出的细胞因子——脂联素，把LyP-1分子修饰在其表面赋予纳米微粒靶向识别能力，研发一种集诊断和治疗于一体的高稳定性，高靶向性，安全性更佳的X线成像/药物载送双功能纳米微粒。实现冠心病易损斑块早期预警和治疗，领航冠心病精准化诊疗。

易损斑块是心血管事件防治焦点，其早期预警与治疗是心血管病领域的世界性难题。易损斑块所导致的血管狭窄程度常常不高，普通影像检查只能显示血管狭窄程度，不能有效反映斑块的稳定性，无法预警心血管事件的真正元凶。虽然OCT可识别易损斑块，但检查有创、价格昂贵、基层医院难以普及。纳米载体可实现易损斑块的早期诊疗。本项目拟利用介孔硅载体，纳米金偶联于载体表面，内腔负载介导胆固醇流出的细胞因子——脂联素，把LyP-1分子修饰在其表面赋予纳米微粒靶向识别能力，研发一种集诊断和治疗于一体的高稳定性，高靶向性，安全性更佳的X线成像/药物载送双功能纳米微粒，实现冠心病易损斑块早期预警和治疗，突破冠心病的精准化诊疗。.经过4年的研究发现，纳米金颗粒的CT显影结果不是特别理想，探索了其他显影剂的种类，采用钆剂进行MRI显影。另外，经实验发现，LyP-1的靶向作用没有HA好，因此采用HA作为靶向分子替代LyP-1，与易损斑块上的内皮细胞表面的CD44结合，使纳米颗粒可以通过HA与CD44结合，携带脂联素与钆剂胞吞入斑块内，实现显影和逆转斑块的治疗目的。药物静脉注射后，自动靶向富集至病变局部，使局部药物浓度比口服药物增加百倍，可以使造影剂和治疗药物靶向聚集，实现易损斑块的诊断和治疗作用。科学意义：（1）动脉粥样硬化是全球的第一大慢性疾病，也是第一大杀手。心肌梗死，脑卒中等，每年夺走无数人的生命；（2）当前药物治疗只能延缓斑块进展，不能有效逆转班块；支架植入及外科搭桥治疗方式有创，且易出现并发症，终身需要抗血小板治疗，增加出血风险；（3）本产品从根本上解决目前药物治疗的局限性，替代介入及外科手术治疗。.目前已经发表SCI论文3篇，获批PCT发明专利10项。并且进入产业化阶段，已经进行成果转化，并进行股权融资2.6亿，组建药物研发团队50人，建立主动靶向纳米制剂研发中心及生产中心。近日提交美国IND（临床批件），获得美国FDA的加速审批。