Synthesis, characterization and self-assembly behavior of zwitterionic amphiphilic triblock copolymers bearing pendant amino acid residues

Abstract

Zwitterionic amphiphilic triblock copolymers bearing pendant amino acid residues poly(allyl glycidyl ether)/cysteine-b-poly(ε-caprolactone)-b-polyethylene glycol (PAGE/cys-b-PCL-b-PEG) were successfully synthesized via a combination of ring-opening polymerization (ROP), condensation reaction and click reaction. The composition and structure of these copolymers were characterized by gel permeation chromatography (GPC) and ¹H nuclear magnetic resonance (¹HNMR) spectroscopy. The self-assembly behavior of the copolymers was investigated by fluorescence (FL), low temperature transmission electron microscopy (cryo-TEM), dynamic light scattering (DLS) and zeta potential. The CMC was 0.20 mg mL⁻¹ (PAGE_3k/cys-b-PCL_6k-b-PEG_3.5k) and 0.47 mg mL⁻¹ (PAGE_1k/cys-b-PCL_3k-b-PEG_2k). The copolymers could self-assemble into spherical micelles with diameters of 26 nm (PAGE_3k/cys-b-PCL_6k-b-PEG_3.5k) and 19 nm (PAGE_1k/cys-b-PCL_3k-b-PEG_2k). Doxorubicin (DOX), an anticancer drug, was encapsulated into the micelles to evaluate the drug release ability. The biocompatibility of these copolymers was evaluated with relatively lower cytotoxicity. Therefore, these zwitterionic amphiphilic triblock copolymers are expected to emerge as promising nanocarriers for various drug deliveries.