Thermo- and pH-Responsive, Coacervate-Forming Hyperbranched Poly(β-amino ester)s for Selective Cell Binding

We report a new type of thermo- and pH-responsive, coacervate-forming highly degradable polymer-hyperbranched poly(β-amino esters) (HPAEs) and its selective cell binding behaviors. The HPAEs were synthesized from 5-amino-1-pentanol (S5) and trimethylolpropane ethoxylate triacrylate (TMPETA) via an A2+B3 type Michael addition. The existence of multiple hydrogen bond pairs as well as tertiary amines makes the S5-TMPETA polymers manifest temperature- and pH-dependent phase transition. By varying the length of the ethylene glycol (EG) spacers in the TMPETA, polymer molecular weight, concentration, and pH value, the phase transition of the S5-TMPETA can be easily tuned in aqueous and buffer solutions, as evidenced by UV-vis spectroscopy and DLS measurements. Especially, the S5-TMPETA prepared from S5 and trimethylolpropane ethoxylate triacrylate 692 (S5-TMPETA692) shows a lower critical solution temperature (LCST) around 33 °C, above which the S5-TMPTEA can form coacervate particles able to encapsulate functional molecules effectively. Importantly, when incubation with HeLa cells, the S5-TMPTETA692 exhibits a temperature- and pH-responsive selective cell binding behaviors. In addition, the S5-TMPETA are highly hydrolyzable and elicit negligible cytotoxicity. This new type of "smart" polymer should find use in a variety of biomedical applications.