PDEAEMA-based pH-sensitive amphiphilic pentablock copolymers for controlled anticancer drug delivery

Abstract

The synthesis of a series of PDEAEMA-based pH-sensitive amphiphilic pentablock copolymers poly(methyl methacrylate)-b-poly(2-(diethylamino)ethyl methacrylate)-b-poly(ethylene glycol)-b-poly(2-(diethylamino)ethyl methacrylate)-b-poly(methyl methacrylate) [PEG-b-(PDEAEMA-b-PMMA)₂] with different compositions proceeded via the combination of a bromination reaction and continuous activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP). All the copolymers were characterized by ¹H NMR and gel permeation chromatography (GPC). The amphiphilic copolymers can self-assemble into micelles in aqueous solution, and the CMC values were comparatively low (2.40–2.80 mg L⁻¹). The pK_b buffering region, particle sizes, zeta potentials and optical transmittance were measured to investigate the pH-sensitivity of the polymeric micelles. The size and morphology of the self-assembled blank and DOX-loaded micelles were determined by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The in vitro release rate was sharply increased by decreasing the pH from 7.4 to 5.0, due to the swelling of micelles at lower pH caused by the protonation of tertiary amine groups of PDEAEMA. The in vitro cytotoxicity of DOX-loaded micelles against Hela cells were measured and compared with free DOX, suggesting that the blank micelles provide low cytotoxicity and the DOX-loaded micelles provided high cytotoxicity nearly that of free DOX. The results indicate that this new kind of amphiphilic copolymers could serve as promising nanocarriers for controlled anticancer drug delivery.