posted on 2016-12-22, 00:00authored byWei Zhang, Zi-Li Yu, Min Wu, Jian-Gang Ren, Hou-Fu Xia, Guo-Liang Sa, Jun-Yi Zhu, Dai-Wen Pang, Yi-Fang Zhao, Gang Chen
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.