Magnetic and Folate Functionalization Enables Rapid Isolation and Enhanced Tumor-Targeting of Cell-Derived Microvesicles
Magnetic and Folate Functionalization Enables Rapid Isolation and Enhanced Tumor-Targeting of Cell-Derived Microvesicles
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磁性和叶酸功能化能够快速分离细胞来源的微泡并增强其肿瘤靶向性
DOI：
10.1021/acsnano.6b05630
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发表时间：
2017-01-01
期刊：
影响因子：
17.1
通讯作者：
Chen, Gang
中科院分区：
文献类型：
--
作者：
Zhang, Wei;Yu, Zi-Li;Chen, Gang
细胞衍生微囊(MVS)是一种生物来源的纳米尺度的膜结合囊泡，可以在细胞之间传递生物活性分子，最近受到了人们的关注，被用作天然治疗平台。然而，由于缺乏有效的方法来有效分离MVS并方便地调节其靶向性质，基于MV的递送平台的医疗应用受到限制。在这里，我们报告了基于供体细胞辅助的膜修饰策略的磁性和叶酸(FA)修饰的MVS的发展。MVS继承了供体细胞的膜特性，这使得它们可以用自己膜上的生物素和FA进行修饰。通过与链霉亲和素修饰的氧化铁纳米颗粒(SA-IONPs)偶联，可以方便、高效、快速地从供体细胞的培养上清液中分离出MVS。此外，共轭磁性纳米粒子和FA在MVS上具有磁性和配体靶向活性。然后，通过电穿孔直接负载阿霉素，将MVS转化为抗肿瘤递送平台。经修饰的MVS在体外和体内均显示出显著的抗肿瘤效果。综上所述，本研究为同时分离细胞源性微血管并转化为靶向给药纳米载体提供了一种有效和方便的策略，从而促进了天然治疗性纳米平台的发展。
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.