Monobody adapter for functional antibody display on nanoparticles for adaptable targeted delivery applications.
Monobody adapter for functional antibody display on nanoparticles for adaptable targeted delivery applications.
复制标题
DOI：
10.1038/s41467-022-33490-8
复制
发表时间：
2022-10-11
影响因子：
16.6
通讯作者：
Tietjen, G. T.
中科院分区：
文献类型：
--
作者：
Albert, C.;Bracaglia, L.;Koide, A.;DiRito, J.;Lysyy, T.;Harkins, L.;Edwards, C.;Richfield, O.;Grundler, J.;Zhou, K.;Denbaum, E.;Ketavarapu, G.;Hattori, T.;Perincheri, S.;Langford, J.;Feizi, A.;Haakinson, D.;Hosgood, S. A.;Nicholson, M. L.;Pober, J. S.;Saltzman, W. M.;Koide, S.;Tietjen, G. T.
血管内皮细胞（ECs）在许多疾病的病理生理中起着核心作用。使用靶向纳米颗粒（NPs）将治疗药物递送到内皮细胞可以通过提供升高和持续的细胞内药物水平显着提高疗效。然而，在人类环境中实现足够水平的NP靶向仍然是难以捉摸的。在这里，我们通过设计一个单体适配器来克服这一障碍，该适配器以完全保留其抗原结合功能的方式在NP表面上呈现抗体。与使用胺偶联的常规抗体固定相比，该系统将体外培养的内皮细胞的靶向效果提高了1000倍，并且能够将NPs稳健地递送到体外灌注的人肾脏内皮细胞中，这是一种用于器官移植的临床环境。我们的单体适配器还实现了简单的即插即用能力，有助于评估各种目标np。这项技术有可能简化并可能加速ec靶向纳米药物的开发和临床转化。靶向纳米颗粒递送到感兴趣的部位是重要的靶向治疗。在这里，作者使用单体适配器来提高抗体在纳米颗粒上的靶向效率，以正确定向抗体以保持靶向功能，并演示了靶向人肾脏血管内皮的应用。
Vascular endothelial cells (ECs) play a central role in the pathophysiology of many diseases. The use of targeted nanoparticles (NPs) to deliver therapeutics to ECs could dramatically improve efficacy by providing elevated and sustained intracellular drug levels. However, achieving sufficient levels of NP targeting in human settings remains elusive. Here, we overcome this barrier by engineering a monobody adapter that presents antibodies on the NP surface in a manner that fully preserves their antigen-binding function. This system improves targeting efficacy in cultured ECs under flow by >1000-fold over conventional antibody immobilization using amine coupling and enables robust delivery of NPs to the ECs of human kidneys undergoing ex vivo perfusion, a clinical setting used for organ transplant. Our monobody adapter also enables a simple plug-and-play capacity that facilitates the evaluation of a diverse array of targeted NPs. This technology has the potential to simplify and possibly accelerate both the development and clinical translation of EC-targeted nanomedicines. Targeted nanoparticle delivery to sites of interest is important for targeted therapeutics. Here, the authors improve the targeting efficiency of antibodies on nanoparticles using a monobody adapter to correctly orientate the antibody to preserve targeting function and demonstrate application in targeting the vascular endothelium of human kidneys.
登录
查看更多内容
可调节的聚（胺二聚体）聚合物可调性，用于定制的核酸递送和其他生物医学应用。
影响因子：
6.2
作者：
Kauffman AC;Piotrowski-Daspit AS;Nakazawa KH;Jiang Y;Datye A;Saltzman WM
通讯作者：
Saltzman WM
影响因子：
5.6
作者：
Koide, Akiko;Wojcik, John;Gilbreth, Ryan N.;Hoey, Robert J.;Koide, Shohei
通讯作者：
Koide, Shohei
DOI：
10.1111/ajt.13906
发表时间：
2016-11
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
Hosgood SA;Saeb-Parsy K;Hamed MO;Nicholson ML
通讯作者：
Nicholson ML
DOI：
10.1073/pnas.1006611107
发表时间：
2010-09-21
影响因子：
11.1
作者：
Liu, Jin;Weller, Gregory E. R.;Radhakrishnan, Ravi
通讯作者：
Radhakrishnan, Ravi
影响因子：
6.7
作者：
Jeong, Sinyoung;Park, Ji Yong;Jeong, Dae Hong
通讯作者：
Jeong, Dae Hong