title: Electroneutralized amphiphilic triblock copolymer with a peptide dendron for efficient muscular gene delivery.
abstract: Hydrophilic-hydrophobic-hydrophilic triblock copolymers, such as Pluronic L64, P85, and P105, have attracted more attention due to their enhancement in muscular gene delivery. In the present study, a new kind of electroneutralized triblock copolymer, LPL, dendron G2(L-lysine-Boc)-PEG2k-dendron G2(L-lysine-Boc), was designed and investigated. This hydrophobic-hydrophilic-hydrophobic copolymer is composed of a structure reverse to that of L64, one of the most effective materials for intramuscular gene delivery so far. Our results showed that LPL exhibited good in vivo biocompatibility after intramuscular and intravenous administration. LPL mediated higher reporter gene expression than L64 in assays of β-galactosidase (LacZ), luciferase, and fluorescent protein E2-Crimson. Furthermore, LPL-mediated mouse growth hormone expression significantly accelerated mouse growth within the first 10 days. Altogether, LPL-mediated gene expression in skeletal muscle exhibits the potential of successful gene therapy. The current study also presented an innovative way to design and construct new electroneutralized triblock copolymers for safe and effective intramuscular gene delivery.
authors.affiliation: National Engineering Research Center for Biomaterials, Sichuan University , Chengdu 610064, China.
authors.forename: Linyu
authors.initials: L
authors.lastname: Pu
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Geng
authors.forename: Sijia
authors.initials: S
authors.lastname: Liu
authors.forename: Jianlin
authors.initials: J
authors.lastname: Chen
authors.forename: Kui
authors.initials: K
authors.lastname: Luo
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.forename: Zhongwei
authors.initials: Z
authors.lastname: Gu
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000737:chemistry*; D001835:Body Weight; D002462:Cell Membrane / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D055664:Electrochemical Techniques / Q000379:methods*; D024202:Electrophoretic Mobility Shift Assay; D018014:Gene Transfer Techniques; D007273:Injections, Intramuscular; D008239:Lysine / Q000737:chemistry; D008297:Male; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D055672:Static Electricity; D013501:Surface-Active Agents / Q000737:chemistry*; D019076:Transgenes
chemical_list: D000873:Anthracenes; D010455:Peptides; D011108:Polymers; D013501:Surface-Active Agents; C501244:dendron; D004247:DNA; D008239:Lysine
keywords: amphiphilic; electroneutralization; gene delivery; pluronics; triblock copolymer