工程化 NIR-II 纳米粒子标记的外泌体用于 缺血心肌细胞的修复

心肌梗死是一种死亡率极高、危害大的疾病。随着现代医学发展，急 性心肌梗死的死亡率得到降低，但梗死期间造成不可逆的功能性心肌细胞 凋亡增加了相关心血管疾病发病率，患者仍面临病情反复甚至加重的风险， 因此对于功能性心肌细胞的修复成为当前的研究热点问题。人源诱导的多 功 能 干 细 胞 分 化 的 间 充 质 干 细 胞 （ Induced pluripotent stem cell-derived mesenchymal stem cells，iMSC）作为一种可靠的干细胞来源，由于其增殖 分化能力优异、免疫排斥反应低等优势，在心肌修复领域十分具有应用潜 力。外泌体（Exosome，Exo）在干细胞修复心肌的过程中起着至关重要的 作用，降低了传统干细胞再生疗法中癌变的风险、提升了心肌细胞转化率。 干细胞外泌体的临床应用仍面临较大的挑战，比如外泌体生物分布、生理 功能的机制等关键问题仍有待研究。因此，通过各种成像手段辅助外泌体 进行心肌修复在基础研究与临床应用中尤为重要 。近红外二区（ Near Infrared-Ⅱ，NIR-Ⅱ）荧光成像技术兼备了高分辨率、组织穿透深度深、灵 敏度高等优点，因此在生物体内成像研究方面具有广泛的应用前景。在这 项研究里，我们提取了 iMSC 的外泌体（iMSC-Exo），对 NIR-Ⅱ探针进行工 程化处理，获得携带心肌修复相关的 MicroRNA 19a（miR-19a）的纳米粒 子，分别验证了外泌体和纳米粒子对心肌细胞的修复作用。同时在纳米粒 子内装载了氧化铁颗粒，通过外部磁场的作用有效增加心肌细胞摄取纳米 粒子标记外泌体。在细胞和动物模型中，我们初步验证了磁引导的可行性。 通过这项研究，我们创新性的设计并验证了工程化 NIR-Ⅱ纳米粒子标 记外泌体的方案，结合多种表征手段分析标记效率，为外泌体在心肌梗死 的治疗应用打下坚实基础。提出并验证了通过工程化 NIR-Ⅱ纳米粒子提升 外泌体治疗和靶向效果的方案，为生物医学领域研究和临床治疗提供了先 进的技术和解决策略。

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