Functional siRNA Delivery by Extracellular Vesicle-Liposome Hybrid Nanoparticles
Functional siRNA Delivery by Extracellular Vesicle-Liposome Hybrid Nanoparticles
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DOI：
10.1002/adhm.202101202
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发表时间：
2021-08-11
影响因子：
10
通讯作者：
Vader, Pieter
中科院分区：
文献类型：
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作者：
Evers, Martijn J. W.;van de Wakker, Simonides, I;Vader, Pieter
由于siRNA分子不能到达它们的作用部位，即靶细胞的胞浆，所以RNA干扰的治疗用途受到限制。脂质纳米粒，包括脂质体，通常被用作siRNA载体系统来克服这一障碍，尽管由于缺乏传递效率，它们的广泛使用仍然受到限制。最近，自然界自己的RNA载体，细胞外小泡(EVS)，由于其固有的性质，越来越多地被认为是替代的siRNA输送工具。然而，它们很难装载外来货物。在这里，制备了EV-脂质体杂化纳米粒(杂化纳米粒)，并对其作为一种结合了脂质体和EVS性质的替代给药系统进行了评价。结果表明，杂交物是包裹siRNA的球形颗粒，含有EV表面标志物，并在功能上向不同类型的细胞递送siRNA。与脂质体相比，杂交体在细胞摄取、毒性和基因沉默效率方面的功能行为发生了变化，并因受体细胞类型的不同而不同。此外，用心脏前体细胞(CPC)衍生的EV产生的杂交细胞保留了CPC-EV的功能特性，如激活内皮细胞信号和迁移。总之，杂交体结合了合成和生物给药系统的优点，可能成为未来siRNA的治疗性载体。
The therapeutic use of RNA interference is limited by the inability of siRNA molecules to reach their site of action, the cytosol of target cells. Lipid nanoparticles, including liposomes, are commonly employed as siRNA carrier systems to overcome this hurdle, although their widespread use remains limited due to a lack of delivery efficiency. More recently, nature's own carriers of RNA, extracellular vesicles (EVs), are increasingly being considered as alternative siRNA delivery vehicles due to their intrinsic properties. However, they are difficult to load with exogenous cargo. Here, EV-liposome hybrid nanoparticles (hybrids) are prepared and evaluated as an alternative delivery system combining properties of both liposomes and EVs. It is shown that hybrids are spherical particles encapsulating siRNA, contain EV-surface makers, and functionally deliver siRNA to different cell types. The functional behavior of hybrids, in terms of cellular uptake, toxicity, and gene-silencing efficacy, is altered as compared to liposomes and varies among recipient cell types. Moreover, hybrids produced with cardiac progenitor cell (CPC) derived-EVs retain functional properties attributed to CPC-EVs such as activation of endothelial signaling and migration. To conclude, hybrids combine benefits of both synthetic and biological drug delivery systems and might serve as future therapeutic carriers of siRNA.