Next generation antimicrobial polymers

抗生素的发展是我们社会的一个重要里程碑，它推动了现代医学的发展。耐多药病原体的迅速发展正在危及这些成就，并被世界卫生组织称为“对健康和人类发展的重大威胁”。新型抗生素的不断减少，加上越来越多的耐多药细菌感染，导致人类进入后抗生素时代，危及现代医学的进步。对抗这些发展的一种方法是使用膜活性物质进行感染治疗，因为它们极不可能受到细菌耐药性的影响。这种系统的天然原型是抗菌肽，它是先天免疫系统的一部分。然而，这些生物分子具有固有的可降解性，在病原和宿主细胞之间的选择性有限，并具有免疫调节特性。为了克服这些问题，研究人员开发了抗菌肽的聚合物模拟物，它具有能够破坏细胞膜的阳离子和疏水单元。然而，到目前为止，还没有找到理想的设计策略，它们的选择性仍然是一个主要问题，限制了它们在临床研究中的适用性。该提案旨在通过模仿迄今尚未考虑的抗菌肽的特性来开发下一代抗菌聚合物。这涉及到由多个抗菌构建块组成的瓶刷共聚物的创建。共价瓶刷和超分子纤维有待开发，其膜活性亚基的多价显示有望提高其活性。此外，这些材料中功能亚基的分割将有系统地变化，因为这个参数已被证明对它们的活性和选择性至关重要。此外，将开发主动靶向策略，将抗菌聚合物的活性集中在感染部位，此外，增加它们对特定病原体的选择性。最后，将开发多种不同系统的组合疗法，以揭示材料之间潜在的协同效应。在抗菌聚合物中引入新的特性和概念将提高它们的性能，并将使它们更接近应用。因此，通过补充甚至替代传统的抗微生物疗法，这些系统将有助于解决抗微生物药物耐药性问题。

The development of antibiotics is one of the major milestones of our society and enabled the development of modern medicine. The rapid progression of multi-drug resistant pathogens is jeopardizing these achievements and has been labelled a "major threat to health and human development" by the world health organization. The steady decrease in new antibiotics in combination with a growing number of infections by multi-drug resistant bacteria leads humanity into the direction of a post-antibiotic era, endangering the advances of modern medicine.One way to counteract these developments is the use of membrane active substances for infection treatment, as they are highly unlikely to be affected by bacterial resistance. The natural prototypes for such systems are antimicrobial peptides, which are part of the innate immune system. However, these biomolecules suffer from their inherent degradability, limited selectivity between pathogenic and host cell, and possess immune-regulatory properties. To overcome these issues, researchers have developed polymeric mimics of antimicrobial peptides, which possess cationic as well as hydrophobic units able to disrupt cellular membranes. However, no ideal design strategy has been found so far, and their selectivity remains a major issue, limiting their suitability for e.g. clinical studies.This proposal aims at developing the next generation of antimicrobial polymers by mimicking properties of antimicrobial peptides that have not been considered so far. This involves the creation of bottle brush copolymers that consist of multiple antimicrobial building blocks. Covalent bottle brushes, as well as supramolecular fibers are to be developed and their multivalent display of membrane active sub-units is envisioned to increase their activity. In addition, the segmentation of functional subunits within those materials will be varied systematically as this parameter has been shown to be of paramount importance for their activity and selectivity. Furthermore, active targeting strategies will be developed to concentrate the activity of antimicrobial polymers at the site of the infection and, in addition, increase their selectivity for specific pathogens. Finally, combinatorial therapies of multiple different systems will be developed to reveal potential synergistic effects between the materials.The introduction of new features and concepts in antimicrobial polymers will boost their performance and will bring them closer to an application. Thus, by supplementing or even substituting conventional antimicrobial therapies, these systems will help to solve the issue of antimicrobial resistance.