3 years ago

Remote Loading of Small-Molecule Therapeutics into Cholesterol-Enriched Cell-Membrane-Derived Vesicles

Remote Loading of Small-Molecule Therapeutics into Cholesterol-Enriched Cell-Membrane-Derived Vesicles
Diana Dehaini, Mengchun Chen, Yijie Chen, Xinxin Zhang, Weiwei Gao, Jia Zhuang, Yue Zhang, Yao Jiang, Pavimol Angsantikul, Qiangzhe Zhang, Liangfang Zhang, Man Ying, Ronnie H. Fang, Xiaoli Wei
The increasing popularity of biomimetic design principles in nanomedicine has led to therapeutic platforms with enhanced performance and biocompatibility. This includes the use of naturally derived cell membranes, which can bestow nanocarriers with cell-specific functionalities. Herein, we report on a strategy enabling efficient encapsulation of drugs via remote loading into membrane vesicles derived from red blood cells. This is accomplished by supplementing the membrane with additional cholesterol, stabilizing the nanostructure and facilitating the retention of a pH gradient. We demonstrate the loading of two model drugs: the chemotherapeutic doxorubicin and the antibiotic vancomycin. The therapeutic implications of these natural, remote-loaded nanoformulations are studied both in vitro and in vivo using animal disease models. Ultimately, this approach could be used to design new biomimetic nanoformulations with higher efficacy and improved safety profiles. Remotely loaded RBC vesicles are fabricated by enriching the naturally derived cell membrane with additional cholesterol. Two model drugs, doxorubicin and vancomycin, are successfully loaded and show efficacy in animal models of disease. The reported approach may pave the way for biomimetic nanoformulations with high potency and safety.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/anie.201707598

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