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外泌体功能与临床应用研究进展

时间:2022-04-08 08:14:21 浏览次数:

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z׽|.է  ]u}0*&y؜jVtwRr'qt@$vo}vi4	r'QQ]thhn63Lޞh4	^|jWG_ۖ基础的诊断使得在癌症病情发展过程中可及时监测分子标志物的变化,这种基于血液样本的检测比重复的组织活检更容易收集样本,更易监控疾病的进展。

2.3 作為药物传输的载体

外泌体表面表达各种粘连蛋白(跨膜蛋白和整合素)能够促进膜的相互作用和膜融合。用PEG-AA载体修饰装载有紫杉醇的外泌体[26],将改善药物在血液中的循环时间并能够靶向肺转移的肿瘤细胞。Dong等[27]发现来自正常人的血清和肌管细胞的外泌体能够携带(dysferlin,DYSF)蛋白到达DYSF敲除的小鼠细胞中,为蛋白缺陷或缺失造成的病症提供了新的治疗策略。利用间充质干细胞的归巢能力,同时工程化修饰细胞分泌富含miR-379的胞外囊泡,作为转移性乳腺癌的创新疗法[28]。细胞外囊泡被嵌入到植入式生物材料中[29],旨在利用酶前体药物疗法实现局部治疗的药物递送。基于RNA的疗法,将抗体样(即Y形状)RNA纳米颗粒附着到微泡上可以有效地将RNA治疗剂特异性地递送给癌细胞[30]。外泌体作为具有生物活性的在细胞间进行物质传递的系统,具有成为治疗药物载体的巨大潜力。

3 展望

在正常生理过程中外泌体发挥着介导细胞间通讯的重要功能[31],它们也能够调节宿主-病原体的相互作用[32],参与传染性疾病、炎性疾病、神经疾病和癌症等多种疾病的病理过程,可作为干预及治疗的潜在新靶点。随着对外泌体研究的深入,外泌体在临床医学中有十分光明的应用前景,主要是因为它们携带有核酸和蛋白,有丰富的生物标志物,可用于监测临床状态、疾病进展、治疗反应等。同时由于它们具有递送生物分子的功能,可作为理想的药物传递载体,通过将分子包裹在胞膜内,可以保护酶或者RNA免于降解,并通过细胞内吞作用来促进细胞摄取。在再生医学应用方面,与干细胞相比,外泌体体积更小,复杂性更低,易于生产和存储,甚至更容易避免干细胞研究应用面临的一些监管问题,同时干细胞外泌体不存在形成肿瘤的风险。此外,由于膜结合蛋白含量较低,外泌体的免疫原性低于干细胞。相信在不远的将来,基于外泌体本身的生理及病理功能可将外泌体应用于疾病的诊断与治疗,为患者带来福音。目前,外泌体的功能还没有完全阐明,外泌体内携带的蛋白与核酸具有不确定性,外泌体与受体细胞的相互作用方式仍然不明确,这一系列问题都有待于科研人员的进一步探索。

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(收稿日期:2018-04-28 本文編辑:封 华)

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