The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine of Ministry of Education, School and Hospital of Stomatology, Wuhan University , Wuhan 430079, P. R. China.
Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University , Wuhan 430079, P. R. China.
ACS Nano. 2017 Jan 24;11(1):277-290. doi: 10.1021/acsnano.6b05630. Epub 2017 Jan 3.
Cell-derived microvesicles (MVs), which are biogenic nanosized membrane-bound vesicles that convey bioactive molecules between cells, have recently received attention for use as natural therapeutic platforms. However, the medical applications of MV-based delivery platforms are limited by the lack of effective methods for the efficient isolation of MVs and the convenient tuning of their targeting properties. Herein, we report the development of magnetic and folate (FA)-modified MVs based on a donor cell-assisted membrane modification strategy. MVs inherit the membrane properties of their donor cells, which allows them to be modified with the biotin and FA on their own membrane. By conjugating with streptavidin-modified iron oxide nanoparticles (SA-IONPs), the MVs can be conveniently, efficiently, and rapidly isolated from the supernatant of their donor cells using magnetic activated sorting. Moreover, the conjugated magnetic nanoparticles and FA confer magnetic and ligand targeting activities on the MVs. Then, the MVs were transformed into antitumor delivery platforms by directly loading doxorubicin via electroporation. The modified MVs exhibited significantly enhanced antitumor efficacy both in vitro and in vivo. Taken together, this study provides an efficient and convenient strategy for the simultaneous isolation of cell-derived MVs and transformation into targeted drug delivery nanovectors, thus facilitating the development of natural therapeutic nanoplatforms.
细胞衍生的微泡（MVs）是一种生物源性纳米尺寸的膜结合囊泡，能够在细胞间传递生物活性分子，最近因其作为天然治疗平台而受到关注。然而，基于 MV 的递药平台的医学应用受到缺乏有效方法来高效分离 MVs 和方便调整其靶向特性的限制。在此，我们报告了一种基于供体细胞辅助膜修饰策略的磁性和叶酸（FA）修饰的 MVs 的开发。MVs 继承了其供体细胞的膜特性，使其能够在自身膜上修饰生物素和 FA。通过与链霉亲和素修饰的氧化铁纳米颗粒（SA-IONPs）缀合，MVs 可以使用磁激活分选从供体细胞的上清液中方便、高效和快速地分离出来。此外，连接的磁性纳米颗粒和 FA 赋予 MVs 磁性和配体靶向活性。然后，通过电穿孔直接装载阿霉素，将 MVs 转化为抗肿瘤递药平台。修饰后的 MVs 在体外和体内均显示出显著增强的抗肿瘤功效。总之，本研究为同时分离细胞衍生的 MVs 并将其转化为靶向药物递药纳米载体提供了一种高效便捷的策略，从而促进了天然治疗纳米平台的发展。
