title: Linear polycations by ring-opening polymerization as non-viral gene delivery vectors.
abstract: For a clinically effective non-viral gene delivery system, a non-toxic and highly efficient vector is of great importance. A series of linear cationic polymers were synthesized by the ring-opening polymerization between diglycidyl ethers and diamines. Their structure-activity relationships as gene delivery vectors were systematically studied. Besides the amino groups with various densities, these polymers have uniform distribution of hydroxyl groups, which were formed in the polymerization and may benefit their biocompatibility and serum-tolerance. These polymers have good DNA binding ability and could condense DNA into nanoparticles with proper sizes and zeta-potentials. MTT assay revealed that polyplexes formed from title polymers have lower cytotoxicity than that derived from PEI. Most of the polymers have higher transfection efficiency than 25 kDa PEI in the in vitro transfection experiments. Polymers prepared from diglycidyl ethers with less or no N atom (2a and 2b) gave dramatically decreased TE, indicating that secondary amine on the backbone is highly required for efficient gene transfection, and compound 2 may be a good building block in the design of cationic polymers for gene delivery. More importantly, these polymers showed much better serum tolerance. Unlike PEI, the transfection mediated by P5 was seldom affected by the presence of 10% serum. Cellular uptake and intracellular distribution studies also confirmed the good performance of P5 in the transfection process with serum.
authors.affiliation: Key Laboratory of Green Chemistry and Technology (Ministry of Education), College of Chemistry, Sichuan University, Chengdu 610064, PR China.
authors.forename: Qin-Fang
authors.initials: QF
authors.lastname: Zhang
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Yi
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.forename: Ji
authors.initials: J
authors.lastname: Zhang
authors.forename: Laifeng
authors.initials: L
authors.lastname: Ren
authors.forename: Qian-Ming
authors.initials: QM
authors.lastname: Chen
authors.forename: Liandi
authors.initials: L
authors.lastname: Guo
authors.forename: Xiao-Qi
authors.initials: XQ
authors.lastname: Yu
mesh_terms: D002021:Buffers; D016923:Cell Death; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism; D004587:Electrophoresis, Agar Gel; D004705:Endocytosis; D004852:Epoxy Compounds / Q000737:chemistry; D004996:Ethidium / Q000378:metabolism; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008970:Molecular Weight; D010316:Particle Size; D010957:Plasmids / Q000378:metabolism; D011073:Polyamines / Q000737:chemistry*; D000071228:Polyelectrolytes; D011094:Polyethyleneimine / Q000138:chemical synthesis / Q000737:chemistry; D058105:Polymerization; D055672:Static Electricity; D014162:Transfection; D014780:Viruses
chemical_list: D002021:Buffers; D004247:DNA; D004852:Epoxy Compounds; D004996:Ethidium; D049452:Green Fluorescent Proteins; D008156:Luciferases; D011073:Polyamines; D000071228:Polyelectrolytes; D011094:Polyethyleneimine; C485184:enhanced green fluorescent protein