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Glycopolymers/PEI complexes as serum-tolerant vectors for enhanced gene delivery to hepatocytes

Zhao, Liman, Li, Yanchun, Pei, Danfeng, Huang, Qingrong, Zhang, Hongwei, Yang, Zechuan, Li, Fan, Shi, Tongfei
Carbohydrate polymers 2019 v.205 pp. 167-175
blood serum, composite polymers, cytotoxicity, ethyleneimine, galactose, genes, hepatocytes, human cell lines, nanoparticles, plasmids, polymerization, protein synthesis, transfection
Serum stability is a crucial factor for ideal polymeric gene vectors. In this work, a series of serum-tolerant and low-toxicity glycopolymers/poly(ethyleneimine) (PEI) complexes were designed for gene delivery. Atomic transfer radical polymerization (ATRP) was used to synthesize the comb-shaped random copolymers dextran-g-poly(2-dimethylaminoethyl methacrylate-co-2-lactobionamidoethyl methacrylate) (DDrL). Then DDrLs/PEI were investigated for their use as plasmid DNA (pDNA) vectors, which can completely condense the pDNA into nanoparticles. The DDrLs/PEI/pDNA complexes in serum-containing media showed better stability than PEI/pDNA complexes. in vitro gene transfection studies showed that DDrLs/PEI exhibited a remarkable transfection efficiency enhancement in the presence of serum compared to that in serum-free conditions. Moreover, the transfection level of DDrLs/PEI were two orders of magnitude higher than that of PEI alone in the presence of 30% serum. DDrLs/PEI complexes with galactose enhanced pDNA delivery to hepatocytes, with higher protein expression in ASGPr-presenting HepG2 than in HeLa cells, which lack the receptor. All of the DDrLs/PEI/pDNA complexes had lower cytotoxicity than PEI/pDNA.