Preparation of pH-sensitive CaP nanoparticles coated with a phosphate-based block copolymer for efficient gene delivery

We have synthesized a phosphate-based block copolymer, PEG-b-PMOEP (poly(ethylene glycol)-b-poly(2-methacryloyloxyethyl phosphate)), with a narrow molecular weight distribution (PD = 1.06) by atomic transfer radical polymerization (ATRP), and have constructed calcium phosphate nanoparticles (CaPNs) coated with the block copolymer as an efficient and safe intracellular gene delivery carrier. The phosphate-mimic PMOEP block could be incorporated into the calcium phosphate (CaP) core to entrap pDNA, with the PEG block forming a shell to prevent uncontrolled growth of CaP precipitates and aggregates in physiological fluids. The CaPNs showed high colloidal stability at pH 7.4, but released entrapped pDNA at an endosomal pH of 5.0 through a pH-dependent protonation of phosphate moieties for efficient endosomal escape. The PEG-b-PMOEP/CaP/pDNA nanoparticles, which were formed simply by mixing, exhibited great potential as gene delivery carriers for future gene therapy applications due to their high transfection efficiency, low toxicity, and good stability under physiological conditions. (C) 2012 Elsevier Ltd. All rights reserved.