title: Guanidinylated bioresponsive poly(amido amine)s designed for intranuclear gene delivery.
abstract: Guanidinylated poly(amido amine)s with multiple disulfide linkages (Gua-SS-PAAs) were designed and constructed as nonviral gene carriers. The main chains of these novel carriers were synthesized based on monomers containing guanidino groups (guanidine hydrochloride and chlorhexidine), which could avoid complicated side-chain-modification reactions while introducing the guanidino groups. The synthesized Gua-SS-PAAs polymers were characterized by (1)H nuclear magnetic resonance, molecular weight, and polydispersity. Furthermore, Gua-SS-PAAs polymers were complexed with pDNA, and the properties of the complexes were determined, including entrapment efficiency, particle size, ζ-potential, atomic force microscopy images, stability, DNA complexation ability, reduction sensitivity, cytotoxicity, and transfection efficiency. The new Gua-SS-PAAs carriers exhibited higher transfection efficiency and lower cytotoxicity compared with two widely used gene delivery carriers, polyethylenimine and lipofectamine 2000. Furthermore, the relationship between the side-chain structure and morphological/biological properties was extrapolated, and the results showed that guanidine in the side chain aids in the improvement of transfection efficiency. In addition, the introduction of guanidino group might confer the new carriers with nuclear localization function compared to carriers without it.
authors: School of Pharmacy, Shenyang Pharmaceutical University.
authors: Jiankun
authors: J
authors: Yu
authors: School of Pharmacy, Shenyang Pharmaceutical University.
authors: Jinmin
authors: J
authors: Zhang
authors: School of Pharmacy, Shenyang Pharmaceutical University.
authors: Haonan
authors: H
authors: Xing
authors: School of Pharmacy, Shenyang Pharmaceutical University.
authors: Zhen
authors: Z
authors: Yang
authors: School of Pharmacy, Shenyang Pharmaceutical University.
authors: Cuifang
authors: C
authors: Cai
authors: School of Pharmacy, Shenyang Pharmaceutical University.
authors: Conglu
authors: C
authors: Zhang
authors: School of Pharmacy, Shenyang Pharmaceutical University.
authors: Xiaoyun
authors: X
authors: Zhao
authors: School of Pharmacy, China Medical University, Shenyang, People's Republic of China.
authors: Minjie
authors: M
authors: Wei
authors: School of Pharmacy, Shenyang Pharmaceutical University.
authors: Li
authors: L
authors: Yang
authors: School of Pharmacy, Shenyang Pharmaceutical University.
authors: Pingtian
authors: P
authors: Ding
mesh_terms: D001562:Benzimidazoles / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002710:Chlorhexidine / Q000494:pharmacology; D003538:Cystamine / Q000737:chemistry; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004587:Electrophoresis, Agar Gel; D004705:Endocytosis / Q000187:drug effects; D018014:Gene Transfer Techniques; D019791:Guanidine / Q000737:chemistry*; D006801:Humans; D061986:MCF-7 Cells; D018625:Microscopy, Atomic Force; D008970:Molecular Weight; D010316:Particle Size; D010957:Plasmids / Q000378:metabolism; D011073:Polyamines / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry; D055672:Static Electricity; D014162:Transfection
chemical_list: D001562:Benzimidazoles; C531249:Poly(amidoamine); D011073:Polyamines; D011094:Polyethyleneimine; D004247:DNA; D019791:Guanidine; C017807:bisbenzimide ethoxide trihydrochloride; D003538:Cystamine; D002710:Chlorhexidine
keywords: cytotoxicity; gene carrier; guanidine; nuclear localization; transfection efficiency