title: Water-Soluble Cationic Polyphosphazenes Grafted with Cyclic Polyamine and Imidazole as an Effective Gene Delivery Vector.
abstract: Gene therapy holds immense potential as a future therapeutic strategy for the treatment of numerous genetic diseases which are incurable to date. Nevertheless, safe and efficient gene delivery remains the most challenging aspects of gene therapy. In this study, a series of polyphosphazenes (PPZ) bearing cyclic polyamine and imidazole groups were synthesized and investigated for gene delivery. Agarose gel electrophoresis assays showed that poly(imidazole/1,4,7,10-tetraazyclodocane)phosphazene (Im-PPZ-cyclen) had good binding ability with plasmid DNA (pDNA), yielding positively charged particles with a size around 120-140 nm from a ratio of 10:1 to 5:1 (Im-PPZ-cyclen/pDNA, w/w). The cytotoxicity of Im-PPZ-cyclen assayed by MTT was lower than that of PEI 25 kDa, and was similar to that reported for poly(di-2-dimethylaminoethylamine)phosphazene (poly(di-DMAEA)phosphazene) to some degree. The maximum transfection efficiency of Im-PPZ-cyclen/pDNA complexes against 293 T cells at the ratio of 5:1 (Im-PPZ-cyclen/pDNA, w/w) is close to that of Lipofectamine 2000. The present work may provide a strategy for the design of new cationic polymers with reduced cytotoxicity and be applied to gene delivery as an efficient nonviral vector.
authors.affiliation: The State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology , Beijing 100029, P. R. China.
authors.forename: Chunying
authors.initials: C
authors.lastname: Ma
authors.affiliation: The State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology , Beijing 100029, P. R. China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: The State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology , Beijing 100029, P. R. China.
authors.forename: Changguo
authors.initials: C
authors.lastname: Du
authors.affiliation: The State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology , Beijing 100029, P. R. China.
authors.forename: Baojing
authors.initials: B
authors.lastname: Zhao
authors.affiliation: The State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology , Beijing 100029, P. R. China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: He
authors.affiliation: The State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology , Beijing 100029, P. R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Li
authors.affiliation: The State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology , Beijing 100029, P. R. China.|State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences, Peking University Health Science Center , Beijing 100083, P. R. China.
authors.forename: Renzhong
authors.initials: R
authors.lastname: Qiao
mesh_terms: D002412:Cations; D005822:Genetic Vectors; D057809:HEK293 Cells; D006801:Humans; D018625:Microscopy, Atomic Force; D009943:Organophosphorus Compounds / Q000737:chemistry*; D011073:Polyamines / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D014162:Transfection
chemical_list: D002412:Cations; D009943:Organophosphorus Compounds; D011073:Polyamines; D011108:Polymers; C108974:poly(phosphazene)