BACKGROUND 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. RESULTS 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. CONCLUSIONS This strategy highlights a paradigmatic approach to construct vectors that need precise intracellular delivery for innovative applications.

中文翻译：

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通过改进生物启发的非病毒载体的细胞摄取和细胞内运输来增强转基因应答。

背景技术由于许多障碍限制了基因操作技术，基因治疗仍然是一个重大挑战。对于非病毒传递载体，由于内体或溶酶体中细胞摄取不足和基因降解不足，它们通常会遭受性能不足的困扰。随着遗传货物的传递，克服这些保守的细胞内壁垒的重要性日益提高。结果启动了涉及仿生甘露醇部分的表面功能化非病毒载体，该载体可控制细胞摄取并促进小窝介导的途径和细胞内运输，从而避免了网格蛋白介导的途径内在化的负载基因的酸性和酶溶酶体降解。不同程度的甘露醇部分被锚定在纳米颗粒的表面上，以形成受生物启发的非病毒载体，并且CaP-MA-40在体外和体内均表现出极高的稳定性，微不足道的毒性以及显着增强的转基因表达。结论该策略强调了一种范式的方法来构建需要精确的细胞内递送用于创新应用的载体。