title: Dexamethasone conjugation to polyamidoamine dendrimers G1 and G2 for enhanced transfection efficiency with an anti-inflammatory effect.
abstract: Polyamidoamine (PAM) dendrimers with low generation such as PAM generation 1 (PAMG1) and PAM generation 2 (PAMG2) have been widely used as a gene carrier due to low toxicity, albeit their low transfection efficiency. In this study, dexamethasone was conjugated to PAMG1 and PAMG2 in order to increase the transfection efficiency. In a gel retardation assay, the dexamethasone conjugated PAMG1 and PAMG2 (PAMG1-Dexa and PAMG2-Dexa) retarded plasmid DNA (pDNA) completely at 5:1 and 3:1 weight ratios (polymer:pDNA), respectively. In transfection assays, PAMG1-Dexa and PAMG2-Dexa had the highest transfection efficiency at 20:1 and 10:1 weight ratios, respectively. In addition, PAMG1-Dexa and PAMG2-Dexa had higher transfection efficiencies than PAMG1, PAMG2, PEI25k, and lipofectamine. In a MTT assay, PAMG1-Dexa and PAMG2-Dexa were less cytotoxic than lipofectamine. In addition, PAMG1-Dexa and PAMG2-Dexa decreased the TNF-α level more efficiently than dexamethasone only in the lipopolysaccharide (LPS)-induced Raw264.7 cells. Therefore, PAMG1-Dexa and PAMG2-Dexa may prove to be useful as gene delivery carriers with an anti-inflammatory effect.
authors: Department of Bioengineering, College of Engineering, Hanyang University, 17 Haengdang-dong, Seoul , Republic of Korea.
authors: Jin Young
authors: JY
authors: Kim
authors: Jae Hwan
authors: JH
authors: Ryu
authors: Hyesun
authors: H
authors: Hyun
authors: Hyun Ah
authors: HA
authors: Kim
authors: Joon Sig
authors: JS
authors: Choi
authors: Dong
authors: D
authors: Yun Lee
authors: Taiyoun
authors: T
authors: Rhim
authors: Jeong Hyun
authors: JH
authors: Park
authors: Minhyung
authors: M
authors: Lee
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000737:chemistry*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics; D050091:Dendrimers / Q000008:administration & dosage / Q000737:chemistry*; D003907:Dexamethasone / Q000008:administration & dosage* / Q000737:chemistry*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D057809:HEK293 Cells; D006801:Humans; D008055:Lipids / Q000008:administration & dosage; D051379:Mice; D010957:Plasmids / Q000235:genetics; D011073:Polyamines / Q000008:administration & dosage / Q000737:chemistry*; D014162:Transfection / Q000379:methods*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D000893:Anti-Inflammatory Agents; D050091:Dendrimers; D008055:Lipids; C086724:Lipofectamine; C531249:Poly(amidoamine); D011073:Polyamines; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D004247:DNA