Antimicrobial resistance is an increasingly serious challenge for public health and could result in dramatic negative consequences for the health care sector during the next decades. To solve this problem, antibacterial materials that are unsusceptible toward the development of bacterial resistance are a promising branch of research. In this work, a new type of polymeric antimicrobial peptide mimic featuring a bottlebrush architecture is developed, using a combination of reversible addition–fragmentation chain transfer (RAFT) polymerization and ring-opening metathesis polymerization (ROMP). This approach enables multivalent presentation of antimicrobial subunits resulting in improved bioactivity and an increased hemocompatibility, boosting the selectivity of these materials for bacterial cells. Direct probing of membrane integrity of treated bacteria revealed highly potent membrane disruption caused by bottlebrush copolymers. Multivalent bottlebrush copolymers clearly outperformed their linear equivalents regarding bioactivity and selectivity. The effect of segmentation of cationic and hydrophobic subunits within bottle brushes was probed using heterograft copolymers. These materials were found to self-assemble under physiological conditions, which reduced their antibacterial activity, highlighting the importance of precise structural control for such applications. To the best of our knowledge, this is the first example to demonstrate the positive impact of multivalence, generated by a bottlebrush topology in polymeric antimicrobial peptide mimics, making these polymers a highly promising material platform for the design of new bactericidal systems.

In order to elucidate mechanisms of nanoparticle (NP)-cell interactions, a detailed knowledge about membrane-particle interactions, intracellular distributions, and nucleus penetration capabilities, etc. becomes indispensable. The utilization of NPs as additives in many consumer products, as well as the increasing interest of tailor-made nanoobjects as novel therapeutic and diagnostic platforms, makes it essential to gain deeper insights about their biological effects. Transmission electron microscopy (TEM) represents an outstanding method to study the uptake and intracellular fate of NPs, since this technique provides a resolution far better than the particle size. Additionally, its capability to highlight ultrastructural details of the cellular interior as well as membrane features is unmatched by other approaches. Here, a summary is provided on studies utilizing TEM to investigate the uptake and mode-of-action of tailor-made polymer nanoparticles in mammalian cells. For this purpose, the capabilities as well as limitations of TEM investigations are discussed to provide a detailed overview on uptake studies of common nanoparticle systems supported by TEM investigations. Furthermore, methodologies that can, in particular, address low-contrast materials in electron microscopy, i.e., polymeric and polymer-modified nanoparticles, are highlighted.

In this study, a series of high molar mass poly(2-oxazoline)-based copolymers was synthesized, introducing 2-ethyl-2-oxazoline, ethylene imine, and primary amine bearing monomer units representing a new generation of PEI.