International Journal of Nanomedicine (Dec 2016)
Co-self-assembly of cationic microparticles to deliver pEGFP-ZNF580 for promoting the transfection and migration of endothelial cells
Abstract
Yakai Feng,1–5 Mengyang Guo,1 Wen Liu,1 Xuefang Hao,1 Wei Lu,1 Xiangkui Ren,1,2 Changcan Shi,4,5 Wencheng Zhang6 1Department of Polymer Science and Engineering, School of Chemical Engineering and Technology, Collaborative Innovation Center of Chemical Science and Chemical Engineering (Tianjin), Tianjin University, 2Tianjin University-Helmholtz-Zentrum Geesthacht, Joint Laboratory for Biomaterials and Regenerative Medicine, 3Key Laboratory of Systems Bioengineering of Ministry of Education, Tianjin University, Tianjin, 4Institute of Biomaterials and Engineering, Wenzhou Medical University, 5Wenzhou Institute of Biomaterials and Engineering, CNITECH, CAS, Wenzhou, 6Department of Physiology and Pathophysiology, Logistics University of Chinese People’s Armed Police Force, Tianjin, People’s Republic of China Abstract: The gene transfection efficiency of polyethylenimine (PEI) varies with its molecular weight. Usually, high molecular weight of PEI means high gene transfection, as well as high cytotoxicity in gene delivery in vivo. In order to enhance the transfection efficiency and reduce the cytotoxicity of PEI-based gene carriers, a novel cationic gene carrier was developed by co-self-assembly of cationic copolymers. First, a star-shaped copolymer poly(3(S)-methyl-morpholine-2,5-dione-co-lactide) (P(MMD-co-LA)) was synthesized using D-sorbitol as an initiator, and the cationic copolymer (P(MMD-co-LA)-g-PEI) was obtained after grafting low-molecular weight PEI. Then, by co-self-assembly of this cationic copolymer and a diblock copolymer methoxy-poly(ethylene glycol) (mPEG)-b-P(MMD-co-LA), microparticles (MPs) were formed. The core of MPs consisted of a biodegradable block of P(MMD-co-LA), and the shell was formed by mPEG and PEI blocks. Finally, after condensation of pEGFP-ZNF580 by these MPs, the plasmids were protected from enzymatic hydrolysis effectively. The result indicated that pEGFP-ZNF580-loaded MP complexes were suitable for cellular uptake and gene transfection. When the mass ratio of mPEG-b-P(MMD-co-LA) to P(MMD-co-LA)-g-PEI reached 3/1, the cytotoxicity of the complexes was very low at low concentration (20 µg mL-1). Additionally, pEGFP-ZNF580 could be transported into endothelial cells (ECs) effectively via the complexes of MPs/pEGFP-ZNF580. Wound-healing assay showed that the transfected ECs recovered in 24 h. Cationic MPs designed in the present study could be used as an applicable gene carrier for the endothelialization of artificial blood vessels. Keywords: star-shaped copolymer, microparticles, gene carrier, endothelial cells, transfection, migration
