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Biomimetic Hetero-Multivalent Binding Nanoparticles for Cell Recognition

用于细胞识别的仿生异多价结合纳米颗粒

基本信息

批准号：
201586423
负责人：
Professor Dr. Achim Goepferich
金额：
--
依托单位：
Lehrstuhl für Pharmazeutische Technologie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2011
资助国家：
德国
起止时间：
2010-12-31 至 2020-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/201586423?language=en
关键词：
Biomimetic Hetero Multivalent Binding Nanoparticles

项目摘要

One of the fundamentally attractive properties of nanomaterials is their ability to serve as drug carriers. They can deliver drugs to sites of action that these would not be able to reach based on their physicochemical properties. However, a fundamental problem involved with this strategy is the specificity of recognizing the target cells. Even though a number of principles of nanomaterial interactions with cells have been described in the literature, they hardly allow a nanomaterial to distinguish between the target- and off-target cells that it may have contact to on its way through the organism. Viruses in contrast, which are essentially nanoparticles too, have developed highly sophisticated techniques to cope with the problem of target cell identification. They use several different types of ligands that bind one after another to receptors on the cell surface to confirm its identity. Goal of this project will be to implement this type of biomimetic hetero-multivalent binding in synthetic nanomaterials. We will work on two design strategies. The first will make use of polyethylene glycol tethers of different length to arrange for a delayed visibility of two receptor ligands on the nanoparticle surface. The second rests on the initial recognition of a cell by a ligand and the confirmation of the cell's identity by its ability to activate a proligand on the nanoparticle surface enzymatically. The ultimate goal will be to obtain particles that are internalized exclusively by their target cells. Mesangial cells will serve as therapeutic target. They are responsible for fibrotic processes during diabetic nephropathy the leading cause of end-stage kidney disease. The project is intended to explore the potential of biomimetic particles as a drug carrier for treating a disease for which therapeutic options are hardly available.

纳米材料最吸引人的特性之一是它们作为药物载体的能力。根据它们的物理化学性质，它们可以将药物输送到这些药物无法到达的作用部位。然而，这一策略涉及的一个基本问题是识别目标细胞的特异性。尽管文献中已经描述了纳米材料与细胞相互作用的一些原理，但它们几乎不允许纳米材料区分它在穿过生物体的途中可能接触到的靶细胞和非靶细胞。相比之下，本质上也是纳米粒子的病毒已经开发出高度复杂的技术来应对目标细胞识别的问题。他们使用几种不同类型的配体，一个接一个地与细胞表面的受体结合，以确认其身份。该项目的目标是在合成纳米材料中实现这种仿生的异多价结合。我们将致力于两个设计策略。第一种将利用不同长度的聚乙二醇链来安排两个受体配体在纳米颗粒表面的延迟可见性。第二个依赖于配基对细胞的初始识别，以及通过酶激活纳米颗粒表面的配基的能力来确认细胞的身份。最终目标将是获得仅由其目标细胞内化的粒子。肾小球系膜细胞将成为治疗靶点。它们负责糖尿病肾病期间的纤维化过程，糖尿病肾病是终末期肾病的主要原因。该项目旨在探索仿生颗粒作为药物载体治疗这种几乎没有治疗选择的疾病的潜力。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Nanoparticles Mimicking Viral Cell Recognition Strategies Are Superior Transporters into Mesangial Cells

DOI：
10.1002/advs.201903204
发表时间：
2020-04-22
期刊：
ADVANCED SCIENCE
影响因子：
15.1
作者：
Maslanka Figueroa, Sara;Fleischmann, Daniel;Goepferich, Achim
通讯作者：
Goepferich, Achim

Influenza A virus mimetic nanoparticles trigger selective cell uptake

DOI：
10.1073/pnas.1902563116
发表时间：
2019-05-14
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
影响因子：
11.1
作者：
Figueroa, Sara Maslanka;Veser, Anika;Goepferich, Achim
通讯作者：
Goepferich, Achim

Microfluidic manufacturing improves polydispersity of multicomponent polymeric nanoparticles