Poly(2-Oxazoline)-Based Polyphotoacids: Synthesis, SolutionBehavior, and Cellular Uptake of Multi-ResponsiveIntracellular Transporters

This work describes the first polymeric photoacids based on poly(2-oxazoline)s. The presence of 1-hydroxypyrene units—a photoacid that can increase its acidity upon blue light irradiation through excited-state proton transfer—allows remote control over material polarity and charge. A set of multi-stimuli-responsive polymers was obtained via partial hydrolysis of poly(2-ethyl-2-oxazoline) precursors, followed by functionalization with 6/8-acetoxypyrene-1-sulphonyl chloride. By varying the reagent ratio, complete or partial functionalization of hydrolyzed units can be achieved; in the latter case some remaining polyethyleneimine(PEI) groups can also be realized. Conducted cytotoxicity studies show high viability of selected cell lines, which serves as a first reported confirmation of biocompatibility of polyphotoacids. This was further confirmed via cellular uptake experiments, where the synthesized copolymers show no cell damage after 24 h of incubation. Apart from that, the polyphotoacid with the highest hydroxypyrene content and remaining PEI-units shows the fastest uptake. The same terpolymer also shows a high capacity for hydrophobic drug encapsulation. The obtained results support the prospect of polyphotoacids as materials in the context of intracellular transport.