Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
Key Laboratory of Pharmacology of the State Administration of Traditional Chinese Medicine, Fourth Military Medical University, Xi'an, 710032, China.
J Nanobiotechnology. 2020 Jan 31;18(1):26. doi: 10.1186/s12951-020-0582-z.
Gene therapy remains a significant challenge due to lots of barriers limiting the genetic manipulation technologies. As for non-viral delivery vectors, they often suffer insufficient performance due to inadequate cellular uptake and gene degradation in endosome or lysosome. The importance of overcoming these conserved intracellular barriers is increasing as the delivery of genetic cargo.
A surface-functionalized non-viral vector involving the biomimetic mannitol moiety is initiated, which can control the cellular uptake and promote the caveolae-mediated pathway and intracellular trafficking, thus avoiding acidic and enzymatic lysosomal degradation of loaded gene internalized by clathrin-mediated pathway. Different degrees of mannitol moiety are anchored onto the surface of the nanoparticles to form bio-inspired non-viral vectors and CaP-MA-40 exhibits remarkably high stability, negligible toxicity, and significantly enhanced transgene expression both in vitro and in vivo.
This strategy highlights a paradigmatic approach to construct vectors that need precise intracellular delivery for innovative applications.
由于限制基因操作技术的诸多障碍，基因治疗仍然是一个重大挑战。对于非病毒递送载体，由于内体或溶酶体中细胞摄取不足和基因降解，其性能往往不足。随着遗传物质的传递，克服这些保守的细胞内障碍变得越来越重要。
启动了一种涉及仿生甘露醇部分的表面功能化非病毒载体，它可以控制细胞摄取并促进小窝蛋白介导的途径和细胞内运输，从而避免通过网格蛋白介导的途径内化的负载基因的酸性和酶解溶酶体降解。不同程度的甘露醇部分锚定在纳米颗粒的表面上形成仿生非病毒载体，CaP-MA-40 表现出极高的稳定性、可忽略的毒性以及显著增强的体外和体内转基因表达。
该策略突出了一种构建载体的范例方法，这些载体需要精确的细胞内传递，以实现创新应用。
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