Evaluation of generations 2, 3 and 4 arginine modified PAMAM dendrimers for gene delivery.
It is a matter of concern to develop and design synthetic non-viral gene carriers with high transfection efficiency and low cytotoxicity in gene therapy. Recently, various arginine conjugated dendrimers showed better performance in transfection and greater viability than polyethyleneimine (PEI). In this study, we synthesized and investigated e-PAM-R G2, 3 and 4 which are biodegradable polyamidoamine (PAMAM) dendrimers modified with arginine and compared that with PAMAM-R series containing amide bonds for gene carriers. For plasmid DNA delivery, the transfection efficiency of e-PAM-R G4 was higher than G3 and G2 and similar to PAMAM-R G4 with favorable cell viability. Moreover, they indicated significantly higher suppression of TEL/AML1 protein, maybe due to rapid olidonucleotide (ODNs) release through biodegradability of e-PAM-R. These results suggest that biodegradable and non-toxic e-PAM-R may be useful carriers for the gene including plasmid DNA, antisense ODNs and si-RNA.
Nam
Hye Yeong
HY
School of Chemistry & Molecular Engineering, Seoul National University, Seoul, Republic of Korea.
Hahn
Hwa Jeong
HJ
Nam
Kihoon
K
Choi
Woo-Hyung
WH
Jeong
Yunseong
Y
Kim
Dong-Eun
DE
Park
Jong-Sang
JS
D021581:Active Transport, Cell Nucleus; D001120:Arginine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000378:metabolism* / Q000633:toxicity; D019677:Artificial Gene Fusion; D002467:Cell Nucleus / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D021881:DNA, Catalytic / Q000235:genetics / Q000378:metabolism; D050091:Dendrimers; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D006801:Humans; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D011073:Polyamines / Q000138:chemical synthesis / Q000378:metabolism* / Q000633:toxicity; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D000097764:ETS Translocation Variant 6 Protein
D001120:Arginine; D050676:Core Binding Factor Alpha 2 Subunit; D004247:DNA; D021881:DNA, Catalytic; D050091:Dendrimers; D016376:Oligonucleotides, Antisense; D011073:Polyamines; D050783:Proto-Oncogene Proteins c-ets; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D000097764:ETS Translocation Variant 6 Protein; C104700:PAMAM Starburst; C493728:RUNX1 protein, human