Streiber, M.; Göppert, N.E.; Bachmann, V.; Schulze, B.; Glässer, R.; Anufriev, I.; Schädel, P.; Nischang, I.; Weber, C.; Werz, O.; Schubert, U.S.; Traeger, A.: Tailoring cationic poly(2-oxazoline)s: Minimizing toxicity and immunogenic response for biological applications. Materials Today Chemistry 44 (2025), p. 102549/1-12
10.1016/j.mtchem.2025.102549
Abstract:
The increasing importance and potential of nanomedicine are underscored by the successful use of mRNA vaccines. The safe transport of genetic material as an active ingredient represents a significant challenge, for which lipids have thus far been primarily used as a non-viral alternative. Cationic polymers are capable of binding and transporting their nucleic acid cargo via electrostatic interactions. However, membrane toxicity, immune activation, and limited biocompatibility restrict the application of cationic polymers, particularly for diseases with critical immune statuses. In this study, degradable poly(2-oxazoline) analogues (dPOx) were synthesized via a post-polymerization synthesis route starting from the well-known cationic poly(ethylene imine) (PEI). The dPOx feature varying fractions of primary amino moieties in their side chains. The polymers were characterized in detail using 1H NMR spectroscopy, size exclusion chromatography, IR spectroscopy, titration of the amino moieties, and analytical ultracentrifugation. They exhibited reduced cytotoxicity towards human monocytes and exceptional hemocompatibility. Simultaneously, the polymers successfully delivered short synthetic single-stranded DNA without inducing the release of pro-inflammatory cytokines, a critical factor for the future application of polymers in the field of nanomedicine.