title: The effect of molecular weight, compositions and lectin type on the properties of hyperbranched glycopolymers as non-viral gene delivery systems.
abstract: The architectures of gene delivery vectors, in addition to their molecular weights and compositions, can play a critical role in DNA condensation and hence on their gene expression. In general, branched polymers are superior gene delivery vectors as compared to their linear analogs. This study reports the efficacy of cationic hyperbranched glycopolymers for DNA condensation and gene expression. Hyperbranched glycopolymers of varying molecular weights and compositions are synthesized via reversible addition fragmentation chain transfer (RAFT) process and are further explored for their gene expression in vitro. Galactose-based hyperbranched polymers are compared to glucose-derived hyperbranched polymers for their cellular uptake, toxicity and gene expression. It is found that molecular weight of hyperbranched polymers, and carbohydrate content of copolymers are critical factors in determining the gene expression as well as in imparting the specificity to these novel gene delivery vectors. The galactose-based hyperbranched glycopolymer of ~30 kDa or lower show improved gene expression at varying polymer/plasmid ratios. The incubation of hyperbranched polyplexes in the presence of serum protein show the presence of stable particles and gene expression of these hyperbranched polyplexes is unaffected in the presence of serum proteins. Furthermore, the cellular uptake and gene expression are studied in two different cell lines in the presence of lectins. It is found that polyplexes-lectin conjugates show enhanced cellular uptake in vitro, however their gene expression is cell line and lectin type dependent.
authors.affiliation: Department of Chemical and Materials Engineering and Alberta Ingenuity Centre for Carbohydrate Science, University of Alberta, Edmonton, AB T6G 2G6, Canada.
authors.forename: Marya
authors.initials: M
authors.lastname: Ahmed
authors.forename: Ravin
authors.initials: R
authors.lastname: Narain
mesh_terms: D002412:Cations; D005434:Flow Cytometry; D005690:Galactose / Q000737:chemistry / Q000633:toxicity; D015870:Gene Expression / Q000187:drug effects; D018014:Gene Transfer Techniques; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D007928:Lethal Dose 50; D008027:Light; D018613:Microscopy, Confocal; D008970:Molecular Weight; D037121:Plant Lectins / Q000737:chemistry* / Q000633:toxicity; D011108:Polymers / Q000737:chemistry* / Q000633:toxicity; D011134:Polysaccharides / Q000737:chemistry* / Q000633:toxicity / Q000648:ultrastructure; D011485:Protein Binding / Q000187:drug effects; D012542:Scattering, Radiation; D055672:Static Electricity; D014162:Transfection; D014780:Viruses / Q000187:drug effects
chemical_list: D002412:Cations; D037121:Plant Lectins; D011108:Polymers; D011134:Polysaccharides; C017707:Ricinus communis agglutinin-1; C043696:jacalin; D005690:Galactose