Polyisobutylene-based multi-responsive block copolymer with potent delivery applications

The development of polymeric nanocarriers that respond to multiple external stimuli offers an attractive strategy for controlled delivery applications. Herein,amphiphilic polyisobutylene (PIB) conjugated block copolymers were synthesized by integrating living cationic and reversible addition-fragmentation chain-transfer (RAFT) polymerization techniques. The resulting block copolymers exhibited tunable thermo- and pH-responsive behavior, arising from the tertiary amine-containing N-(2-(diethylamino)ethyl)methacrylamide (DEAEMA) segment. Their phase-transition temperatures were further influenced by sodium chloride (NaCl) and urea, demonstrating sensitivity to the surrounding solution environment. The block copolymers also showed reversible carbon dioxide (CO2) responsiveness, enabling reversible switching of the copolymer’s thermo-responsive behavior through alternating CO2/N2 treatment. The hydrophobic PIB segment promoted spontaneous self-assembly into nanoscale aggregates in aqueous media, as supported by critical aggregation concentration (CAC), dynamic light scattering (DLS), and morphological analyses. Furthermore, Nile red was used as a model hydrophobic dye to assess the delivery behavior of the copolymers under physiologically relevant conditions (pH 5.5 and 37 °C), highlighting their potential as multi-functional nanocarriers for stimuli-triggered delivery applications.