Biomimetic Polymers with Reversible Cell Adhesive and Cell Resistant Properties, Biological Evaluation, Structural Optimization and Physicochemical Characterization of Finely-Tuned Pairs of Zwitterionic Polymers for Controlled Cell Binding and Release

本项目的目的是对各种超支化两性离子聚合物的可逆生物粘附性进行生物学评价和结构优化。该项目的背景是最近的发现，带有天然磷酰胆碱(PC)生物膜的反向偶极的聚合物--即所谓的胆碱磷酸盐(CP)--表现出可逆的细胞粘附性。CP聚合物的这些性质可能依赖于与脂质双层细胞膜的外叶磷胆碱偶极子的多价相互作用，并且可以通过添加PC修饰的聚合物来逆转。因此推测，与CP两性离子具有相同连续互补电荷排列的其他甜菜碱型两性离子基团，如磺基甜菜碱或羧基甜菜碱，也会观察到可逆的细胞结合性质。多价两性离子聚合物是利用仿生方法设计的，因此是一种很有前途的生物相容性聚合物。在这个项目中，将识别不同的这些聚合物组，它们显示由一种化合物控制的细胞结合，并通过竞争结合将互补化合物与反向偶极添加到细胞中来触发细胞释放。两性离子偶极内阴离子性质的影响将通过体外细胞培养实验进行研究，用于可逆细胞黏附的配套聚甜菜碱组将在结合强度、生物相容性、特别是细胞毒性方面进行结构优化。定义的CP和PC聚合物的低分子类似物将通过等温滴定量热法揭示这种特殊的互补两性离子相互作用的一整套热力学参数。这有助于从根本上更好地理解多价偶极子相互作用。此外，还将评估用不同两性离子基团修饰的硬核纳米颗粒的细胞结合性能，并与各自的软核两性离子聚合物的性能进行比较。因此，它的目的是更深入地了解这些化合物的多价相互作用，这将有助于未来设计这些化合物在生物医学领域的特定应用，其中需要确定的性质，如结合强度或细胞摄取。预计这些聚合物将具有多方面的应用，如新型局部给药系统、组织工程基质或医疗和诊断设备的表面涂层材料。

The aim of this project is the biological evaluation and structural optimization of various hyperbranched zwitterionic polymers for their reversible bioadhesive properties. The background for this project is the recent finding that polymers that bear reversed dipoles of natural phosphorylcholine (PC) based biomembranes - so called choline phosphates (CP) - exhibit reversible cell adhesive properties. These properties of the CP polymer presumably rely on a multivalent interaction with the outer leaflet phoshorylcholine dipoles of the lipid bilayer cell membrane and can be reversed by addition of a PC modified polymer. It is therefore postulated that reversible cell binding properties will also be observed with other betaine based zwitterionic groups such as sulfobetains or carboxybetaines which have the same consecutive arrangement of complementary charges as the CP zwitterions. The multivalent zwitterionic polymers are designed using a biomimetic approach and are therefore promising biocompatible polymers. Within this project distinct sets of these polymers will be identified which show controlled cell binding by one compound and triggered release from the cell by addition of the complementary compound with the reversed dipole via a competitive binding. The influence of the nature of the anions within the zwitterionic dipoles will be studied by in vitro cell culture experiments and matching sets of polybetaines for reversible cell adhesion will be structurally optimized with respect to binding strength, biocompatibility and in particular cell toxicity. Defined low molecular weight analogues of CP and PC polymers will reveal the whole set of thermodynamic parameters of this particular complementary zwitterion interaction via isothermal titration calorimetry. This contributes to a better fundamental understanding of the multivalent dipol-interaction. In addition, hard core nanoparticles modified with variable zwitterionic groups will be evaluated for their cell binding properties and compared to the performance of the respective soft core zwitterionic polymers. Thereby, it is aimed at a deeper mechanistical understanding of the multivalent interaction of these compounds which will help in the future design of such compounds for specific applications in the biomedical field where defined properties such as binding strength or cell uptake are needed. It is expected that these polymers will have multi-facetted applications such as novel localized drug delivery systems, tissue engineering matrices or surface coating materials of medical and diagnostical devices.