PH-triggered unimer/vesicle-transformable and biodegradable polymersomes based on PEG-b-PCL-grafted poly(β-amino ester) for anti-cancer drug delivery

pH-triggered unimer/vesicle-transformable and biodegradable polymersomes based on methoxy-poly(ethylene glycol)-b-poly(ε-caprolactone)-grafted poly(β-amino ester) (PAE-g-PCL-PEG) were prepared without the use of organic solvents to minimize the biological problems and investigated for an efficient acid-targeted drug-delivery system. The graft copolymers were synthesized via the reactions between carboxyl group-terminated PEG-PCL and hydroxyl groups of PAE (M_n = 5.8 kg/mol), and the molecular weight of both PEG and PCL blocks of copolymers was controlled ranging from 1.0 to 2.0 kg/mol. The synthesized copolymer showed biodegradability and low cytotoxicity. To avoid the use of organic solvents, the self-assembly behavior of these copolymers were examined in water by controlling the pH. The size and morphology were determined by dynamic light scattering (DLS), transmission electron microscopy (TEM), and cryogenic TEM. The results exhibited a unimer/vesicle at tumoral/physiological pH values through ionization/deionization of tertiary amines of PAE when copolymer has ∼1 kDa of PCL block. The study on in vitro release of doxorubicin hydrochloride (DOXHCl)-loaded polymersomes showed that this pH-dependant transition triggered the rapid release of encapsulated DOXHCl in a weakly acidic environment. Confocal laser scanning microscope (CLSM) observations revealed rapid release of DOXHCl enhances the cellular uptake of DOXHCl into MCF-7 cells in an acidic condition. Based on the biocompatible characteristics and significantly rapid release of drugs in acidic environment of this system, it would be a useful drug carrier for the cancer therapy.