Dual-Stimuli-Responsive Disassembly and Tunable Cell Interactions of Cationic Poly(2-oxazoline-stat-ethylene Imine) Nanorods

Abstract Poly(2-oxazoline) block copolymers (BCPs) have been demonstrated to undergo fully aqueous, heat-induced “living” seeded crystallization-driven self-assembly (CDSA) to form length-tunable nanorods. Due to their “stealthiness” and biocompatibility, these nanorods demonstrate potential as a drug delivery platform. However, research into drug loading and controlled release remains limited, and opportunities to exploit surface chemistry modification, including charged or other functional motifs, relatively unexplored. In this study, we synthesized poly(2-oxazoline-stat-ethylene imine) copolymers via preferential partial hydrolysis of poly(2-oxazoline) BCPs. These polymers were self-assembled via CDSA to form novel charged nanorods that retained morphology control and crystallinity similar to that of pure poly(2-oxazoline) BCPs. The dissolution kinetics of poly(2-oxazoline-stat-ethylene imine) nanorods showed that introducing secondary amines to the nanorod corona facilitated both temperature- and pH-responsive disassembly. These nanorods were confirmed to be biocompatible and seen to demonstrate an increase in cellular association, which correlated with higher cationic charge, alongside increased internalization toward multiple organelles, including lysosomes and endosomes.