Bio‐Inspired, Zwitterionic Copolymers with Amphiphilic Character

Selectively targeting diseases with therapeutics remains a crucial yet still unsatisfied challenge in (nano)medicine. In recent years, a large body of biologically based drug carrier systems are produced which have proven to be suitable for the efficient transport of active compounds such as biopharmaceuticals and biotechnological drugs. However, those naturally occurring materials often entail risks, for example, due to accessible, functional groups created by uncontrolled protein denaturation processes of enzymes (e.g., proteases) which can lead to unwanted side effects in the body. To deal with this issue, designing bio-inspired synthetic copolymers offers a suitable alternative compared to systems based on materials derived from natural sources. Owing to the variety of electrostatically interacting motifs abundant in nature, synthetic statistical copolymers are developed with different polarity and zwitterionic arginine-derived units. To achieve the required physicochemical demands, a simple one-step synthesis approach is applied, the so-called xanthate-supported photo-iniferter reversible-addition-fragmentation chain-transfer (XPI-RAFT) polymerization. The cellular association of these polymers is compared to a fully non-ionic polymer. The results highlight new findings in the design of zwitterionic macromolecule structures for medical applications and further progress the understanding of the driving forces of the cell specificity of polyzwitterions.