Exosomes as drug delivery vehicles for Parkinson's disease therapy.
Exosomes as drug delivery vehicles for Parkinson's disease therapy.
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外泌体作为帕金森氏病疗法的药物。
DOI：
10.1016/j.jconrel.2015.03.033
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发表时间：
2015-06-10
期刊：
影响因子：
--
通讯作者：
Batrakova EV
中科院分区：
文献类型：
--
作者：
Haney MJ;Klyachko NL;Zhao Y;Gupta R;Plotnikova EG;He Z;Patel T;Piroyan A;Sokolsky M;Kabanov AV;Batrakova EV
外泌体是天然存在的纳米囊泡，在过去几年中作为药物递送载体引起了相当大的关注。外泌体由天然脂质双层组成，具有丰富的粘附蛋白，易于与细胞膜相互作用。我们认为，单核细胞和巨噬细胞分泌的外泌体可以提供前所未有的机会，以避免在单核吞噬细胞（作为宿主免疫系统的一部分）中的截留，同时增强掺入的药物向靶细胞的递送，最终提高药物治疗功效。鉴于此，我们开发了一种新的基于外泌体的递送系统，用于治疗帕金森病（PD）的有效抗氧化剂过氧化氢酶。使用不同的方法将过氧化氢酶离体加载到外来体中：在室温下孵育、用皂苷透化、冻融循环、超声处理或挤出。所获得的负载过氧化氢酶的外泌体（exoCAT）的尺寸在100 - 200 nm的范围内。超声处理和挤压后外泌体的重组，或用皂苷透化，导致高装载效率、持续释放和过氧化氢酶保护以防止蛋白酶降解。外泌体在体外很容易被神经元细胞摄取。鼻内给药后，在PD小鼠脑中检测到相当数量的外泌体。ExoCAT在PD的体外和体内模型中提供显著的神经保护作用。总的来说，基于外来体的过氧化氢酶制剂具有成为治疗炎性和神经退行性疾病的通用策略的潜力。
Exosomes are naturally occurring nanosized vesicles that have attracted considerable attention as drug delivery vehicles in the past few years. Exosomes are comprised of natural lipid bilayers with the abundance of adhesive proteins that readily interact with cellular membranes. We posit that exosomes secreted by monocytes and macrophages can provide an unprecedented opportunity to avoid entrapment in mononuclear phagocytes (as a part of the host immune system), and at the same time enhance delivery of incorporated drugs to target cells ultimately increasing drug therapeutic efficacy. In light of this, we developed a new exosomal-based delivery system for a potent antioxidant, catalase, to treat Parkinson’s disease (PD). Catalase was loaded into exosomes ex vivo using different methods: the incubation at room temperature, permeabilization with saponin, freeze-thaw cycles, sonication, or extrusion. The size of the obtained catalase-loaded exosomes (exoCAT) was in the range of 100 - 200 nm. A reformation of exosomes upon sonication and extrusion, or permeabilization with saponin resulted in high loading efficiency, sustained release, and catalase preservation against proteases degradation. Exosomes were readily taken up by neuronal cells in vitro. A considerable amount of exosomes was detected in PD mouse brain following intranasal administration. ExoCAT provided significant neuroprotective effects in in vitro and in vivo models of PD. Overall, exosome-based catalase formulations have a potential to be a versatile strategy to treat inflammatory and neurodegenerative disorders.
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影响因子：
46.9
作者：
Alvarez-Erviti, Lydia;Seow, Yiqi;Wood, Matthew J. A.
通讯作者：
Wood, Matthew J. A.
影响因子：
--
作者：
AMBANI, LM;VANWOERT, MH;MURPHY, S
通讯作者：
MURPHY, S
影响因子：
3.9
作者：
González-Polo, RA;Soler, G;Fuentes, JM
通讯作者：
Fuentes, JM
影响因子：
6.2
作者：
Armstrong, Jonathan K.;Hempel, Georg;Garratty, George
通讯作者：
Garratty, George
影响因子：
4.7
作者：
Batrakova, Elena V.;Li, Shu;Gendelman, Howard E.
通讯作者：
Gendelman, Howard E.