Zwitterionic Janus Dendrimer with distinct functional disparity for enhanced protein delivery.
Zwitterionic Janus Dendrimer with distinct functional disparity for enhanced protein delivery.
复制标题
两性离子 Janus Dendrimer 具有独特的功能差异，可增强蛋白质递送。
DOI：
10.1016/j.biomaterials.2019.119233
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发表时间：
2019
期刊：
影响因子：
14
通讯作者：
Luo,Juntao
中科院分区：
文献类型：
--
作者：
Wang,Lili;Shi,Changying;Wang,Xu;Guo,Dandan;Duncan,ThomasM;Luo,Juntao
开发一种简便的蛋白质递送载体具有挑战性，并且仍然是临床应用的未满足的需求。纳米载体明确的结构和功能对于再现性和法规遵从性来说是非常理想的。在此，我们首次报道了一种新型 Janus dendrimer (JD) 系统，该系统由两种不同的树突组成，分别具有优异的蛋白质结合和蛋白质排斥特性，可实现有效的自发蛋白质装载和增强的体内蛋白质递送。形成核心的树突与带电和疏水部分的组合相连，它们通过多价和协同相互作用有效地包裹蛋白质表面。反树突上的两性离子外围赋予纳米颗粒（<20nm）高度亲水和防污的表面，如生物层干涉测定法所示，可有效防止血清蛋白吸附和交换，从而减少蛋白质过早释放。令人惊讶的是，与两性离子羧基甜菜碱 (CB)-JD 和聚乙二醇化纳米载体相比，含有仿生甘油磷酸胆碱 (GPC) 表面的 JD 纳米载体显着增强了蛋白质治疗药物的细胞内摄取，特别是在癌细胞中。相对于聚乙二醇化纳米载体，两性离子JD纳米载体大大延长了有效负载的体内药代动力学特征。 Janus纳米载体控制体内胰岛素的释放并改善小鼠的血糖控制。
The development of a facile protein delivery vehicle is challenging and remains an unmet demand for clinical applications. The well-defined structure and functionality of a nanocarrier are highly desirable for the reproducibility and regulatory compliance. Herein, we report for the first time a novel Janus dendrimer (JD) system, comprised of two distinct dendrons with superior protein binding and protein repelling properties, respectively, for efficient spontaneous protein loading and enhancedin vivoprotein delivery. Core-forming dendron is tethered with a combination of charged and hydrophobic moieties, which coat protein surface efficiently via the multivalent and synergistic interactions. Zwitterionic peripheries on the counter dendron endow the nanoparticle (<20 nm) with a highly hydrophilic and antifouling surface, which efficiently prevents serum protein adsorption and exchange as demonstrated in biolayer interferometry assay, therefore, reducing premature protein release. Surprisingly, JD nanocarriers containing biomimicking glycerylphosphorylcholine (GPC) surface significantly enhanced the intracellular uptake of protein therapeutics specifically in cancer cells, compared with zwitterionic carboxybetain (CB)-JD and PEGylated nanocarriers. The zwitterionic JD nanocarriers greatly prolonged thein vivopharmacokinetic profiles of payloads relative to the PEGylated nanocarriers. Janus nanocarrier controlled thein vivorelease of insulin and improved the blood sugar control in mice.