纳米囊泡递送系统在心血管疾病中的应用

Application of the nanovesicle delivery system in cardiovascular diseases

背景:目前心血管疾病治疗的重点主要聚焦于精准治疗,而细胞外囊泡作为天然的纳米递送系统,可将治疗性药物递送至目标位置,鉴于其可获得亲本细胞的某些特性,故有望作为细胞治疗的替代疗法。目的:针对细胞外囊泡作为纳米递送系统对心血管系统疾病作用的研究现状及最新进展做一综述。方法:利用计算机在中国知网和PubMed数据库检索关于细胞外囊泡作为纳米递送系统对心血管系统疾病的相关研究,检索关键词为“细胞外囊泡、仿生囊泡、工程化囊泡、外泌体、微泡、药物递送、载药、纳米系统、心血管疾病、心脏”及“Extracellular vesicle,Bionic vesicle,Engineered vesicles,Exosome,Drug delivery,Nanopartical system,cardiovascular disease,Atherosclerosis,Myocardial infarction,Nano systems”,最终纳入83篇文献进行综述分析。结果与结论:①细胞外囊泡是一种纳米级囊泡,可通过膜融合、受体-配体相互作用模式、细胞内吞或吞噬等多种机制,将携带的生物活性分子从供体细胞转移到受体细胞。②与传统的纳米材料相比,细胞外囊泡具有生物相容性、生物可降解性、低毒性和低免疫原性等优点,在纳米医学中具有巨大的研究意义。③鉴于细胞外囊泡具有可被外周循环单核巨噬系统快速清除的特点,因此,可利用细胞外囊泡经递送内容物的改变、细胞外囊泡膜修饰、融合及生物工程改性等方法,构建出纳米囊泡递送系统,从而使细胞外囊泡逃避免疫清除,提高靶向性。④细胞外囊泡被认为是心血管系统疾病细胞疗法的一种潜在的替代物,也已成为药物释放的纳米平台,它不仅可以避免细胞移植的免疫排斥反应,还可以增加药物的靶向性,减少对其他组织器官的药物毒性。⑤直接将药物负载到细胞外囊泡中可能不能有效地运送到受体细胞内,这可能是由于细胞外囊泡易被外周循环单核巨噬系统吞噬所致;但是由细胞外囊泡经过一定手段构建的纳米囊泡递送系统可以实现免疫逃逸,从而达到靶向治疗的作用,为心血管疾病的精准治疗提供了新手段。⑥纳米囊泡递送系统具有控释特性,在提高药物对心脏缺血事件患者的心脏保护方面具有一定的应用潜力。⑦未来如何通过细胞外囊泡成功构建出纳米囊泡递送系统有效递送治疗性药物靶向心脏具有巨大的研究价值。

BACKGROUND:At present,the focus on cardiovascular disease treatment is mainly on precision treatment.As a natural nano delivery system,extracellular vesicles can deliver therapeutic drugs to the target location.In view of some characteristics of parent cells,it is expected to be used as an alternative therapy for cell therapy.OBJECTIVE:To summarize the research status and latest progress of extracellular nanovesicles delivery system in cardiovascular diseases.METHODS:The computer was used to search the related research of extracellular vesicles and use it as a nano-drug delivery system in databases such as CNKI and PubMed.Chinese and English key words were“extracellular vesicle,bionic vesicle,engineered vesicle,exosome,microvesicle,drug delivery,drug loading,nanopartical system,cardiovascular disease”.Finally,83 articles were included for review and analysis.RESULTS AND CONCLUSION:(1)Extracellular vesicle is a kind of nanovesicles,which can transfer bioactive molecules from donor cells to recipient cells through membrane fusion,receptor ligand interaction mode,endocytosis or phagocytosis and other mechanisms.(2)Compared with traditional nanomaterials,extracellular vesicles have the advantages of biocompatibility,biodegradability,low toxicity and low immunogenicity.They are of great research significance in nanomedicine.(3)In view of the characteristics that it can be quickly cleared by the peripheral circulating mononuclear macrophage system,the nanovesicle delivery system can be constructed by means of the change of the delivery content,the modification of the extracellular vesicle membrane,the fusion and the bioengineering modification of the extracellular vesicles,so that the extracellular vesicles can avoid epidemic clearance and improve the targeting.(4)Extracellular vesicles are considered as a potential substitute for cell therapy,and have also become a nanoplatform for drug releases.It can not only avoid the immune rejection of cell transplantation,but also increase the targeting of drugs and reduce the drug toxicity to other tissues and organs.(5)Direct drug loading into extracellular vesicles may not be able to efficiently deliver to the recipient cells,which may be due to the fact that extracellular vesicles are easily phagocytized by the peripheral circulating mononuclear macrophage system.However,the nanovesicle delivery system constructed by extracellular vesicles through certain means can achieve immune escape,thus achieving the role of targeted therapy,providing a new means for the precise treatment of cardiovascular diseases.(6)The nanovesicle delivery system has a controlled-release property,which has great prospects of improving the cardioprotective potential for drugs for patients with cardiac ischemic events.(7)How to successfully construct a nanovesicle delivery system through extracellular vesicles to effectively deliver therapeutic drugs to the heart has great research values.