title: Gene transfection efficacy and biocompatibility of polycation/DNA complexes coated with enzyme degradable PEGylated hyaluronic acid.
abstract: Coating the polycation/DNA binary complexes with PEGylated polyanions can improve long-circulation and biocompatibility in vivo. However, it has been certificated PEG dilemma can reduces gene transfection efficiency because of inhibition in cellular uptake and endosomal escape. Herein, two PEGylated anionic polymers, PEGylated hyaluronic acid (HgP) and PEGylated polyglutamic acid (PGgP) were synthesized to coat the binary complexes of core-shell cationic polycaprolactone-graft-poly (N, N-dimethylaminoethyl methacrylate) nanoparticles/DNA (NP-D). The effects of polyanion structure were evaluated in terms of particle size, zeta potential, cytotoxicity, cellular uptake and transfect efficiency in vitro and in vivo. In vitro study illustrated that HgP coated complexes showed better efficiencies in both cell uptake and transfection than PGgP coated complexes. The coating of HgP on NP-D improved the biocompatibility without reduction in cell uptake and transfection efficacy, and resulted in higher accumulation and gene expression in tumor after IV injection. The success of HgP coating in overcoming PEG dilemma is attributed to the hyaluronic acid (HA)-receptor-mediated endocytosis and outer shell-detachment through the hyaluronidases catalyzed degradation of HA. These results demonstrated that HgP was a promising anionic polymer for coating the polycation/DNA complexes and ternary complexes (HgP coated NP-D) hold promising potential for cancer therapy.
authors.affiliation: School of Chemical Engineering and Technology, Tianjin University, Key Laboratory of Systems Bioengineering, Ministry of Education of China, Tianjin 300072, China.
authors.forename: Wendi
authors.initials: W
authors.lastname: Zhang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Cheng
authors.forename: Shutao
authors.initials: S
authors.lastname: Guo
authors.forename: Daoshu
authors.initials: D
authors.lastname: Lin
authors.forename: Pingsheng
authors.initials: P
authors.lastname: Huang
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.forename: Tuo
authors.initials: T
authors.lastname: Wei
authors.forename: Liandong
authors.initials: L
authors.lastname: Deng
authors.forename: Zicai
authors.initials: Z
authors.lastname: Liang
authors.forename: Xing-Jie
authors.initials: XJ
authors.lastname: Liang
authors.forename: Anjie
authors.initials: A
authors.lastname: Dong
mesh_terms: D000818:Animals; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism / Q000493:pharmacokinetics; D056945:Hep G2 Cells; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry; D011073:Polyamines / Q000737:chemistry / Q000378:metabolism*; D000071228:Polyelectrolytes; D011091:Polyesters / Q000737:chemistry / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism*; D011099:Polyglutamic Acid / Q000737:chemistry / Q000378:metabolism; D014162:Transfection
chemical_list: D004247:DNA; D006820:Hyaluronic Acid; D011073:Polyamines; D000071228:Polyelectrolytes; D011091:Polyesters; D011092:Polyethylene Glycols; D011099:Polyglutamic Acid; C016240:polycaprolactone