A cationic amphiphilic co-polymer as a carrier of nucleic acid nanoparticles (Nanps) for controlled gene silencing, immunostimulation, and biodistribution
A cationic amphiphilic co-polymer as a carrier of nucleic acid nanoparticles (Nanps) for controlled gene silencing, immunostimulation, and biodistribution
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DOI：
10.1016/j.nano.2019.102094
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发表时间：
2020-01-01
影响因子：
5.4
通讯作者：
Afonin, Kirill A.
中科院分区：
文献类型：
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作者：
Halman, Justin R.;Kim, Ki-Taek;Afonin, Kirill A.
可编程核酸纳米颗粒(NANP)提供治疗性核酸(TNA)和其他生物功能的受控协调。除了多价，最近的报告表明，NANP技术也可以诱导特定的免疫反应，为这种创新的方法增加了另一层可定制性。虽然核酸的输送仍然是一个挑战，但新的载体正在不断地引入和测试。聚合物平台已被证明在保护核酸货物不受核酸酶降解的同时促进其递送和细胞内释放方面是有效的。在这里，我们超越了传统poly-(lactide-co-glycolide)-graft-polyethylenimine的交付，将稳定的阳离子TNA与功能化的NANP相结合。此外，我们比较了几个有代表性的NANP，以评估它们的整体结构如何影响它们与同一运营商的交付。体外和体内对不同制剂的广泛研究表明，它们在免疫刺激活性、基因沉默效率和生物分布方面存在差异，纤维状NANP可促进TNA的传递。(C)2019 Elsevier Inc.保留所有权利。
Programmable nucleic acid nanoparticles (NANPs) provide controlled coordination of therapeutic nucleic acids (TNAs) and other biological functionalities. Beyond multivalence, recent reports demonstrate that NANP technology can also elicit a specific immune response, adding another layer of customizability to this innovative approach. While the delivery of nucleic acids remains a challenge, new carriers are introduced and tested continuously. Polymeric platforms have proven to be efficient in shielding nucleic acid cargos from nuclease degradation while promoting their delivery and intracellular release. Here, we venture beyond the delivery of conventional TNAs and combine the stable cationic poly-(lactide-co-glycolide)-graft-polyethylenimine with functionalized NANPs. Furthermore, we compare several representative NANPs to assess how their overall structures influence their delivery with the same carrier. An extensive study of various formulations both in vitro and in vivo reveals differences in their immunostimulatory activity, gene silencing efficiency, and biodistribution, with fibrous NANPs advancing for TNA delivery. (c) 2019 Elsevier Inc. All rights reserved.