The AGMA1 polyamidoamine mediates the efficient delivery of siRNA

被引：17
作者：
Cavalli, Roberta [1 ]
Primo, Luca [2 ,3 ]
Sessa, Roberto [4 ]
Chiaverina, Giulia [2 ]
di Blasio, Laura [2 ]
Alongi, Jenny [5 ]
Manfredi, Amedea [5 ]
Ranucci, Elisabetta [5 ]
Ferruti, Paolo [5 ]
机构：
[1] Univ Turin, Drug Sci & Technol Dept, Turin, Italy
[2] Candiolo Canc Inst FPO IRCCS, Candiolo, Italy
[3] Univ Turin, Dept Oncol, Turin, Italy
[4] Univ Calif Berkeley, Cardiovasc Res Inst, Berkeley, CA 94720 USA
[5] Univ Milan, Dept Chem, Via C Golgi 19, I-20133 Milan, Italy
来源：
JOURNAL OF DRUG TARGETING | 2017年 / 25卷 / 9-10期
关键词：
Polyamidoamine; AGMA1; siRNA; AGMA1/siRNA polyplexes; intracellular siRNA delivery; gene silencing; GENE-THERAPY; IN-VITRO; PHYSICOCHEMICAL PROPERTIES; POLYELECTROLYTE COMPLEXES; AMPHOTERIC AGMATINE; NONVIRAL VECTORS; VIVO; POLY(AMIDOAMINE)S; PROTEIN; DESIGN;
D O I：
10.1080/1061186X.2017.1363215
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
AGMA1, a prevailingly cationic, guanidine-bearing, linear, amphoteric polyamidoamine is an effective siRNA condensing agent. Here two AGMA1 samples of different molecular weight, i.e. AGMA1-5 and AGMA1-10 were evaluated as siRNA condensing agents and transfection promoters. AGMA1-10 formed stable polyplexes with a size lower than 50 nm and positive zeta potential. AGMA1-5 polyplexes were larger, about 100 nm in size. AGMA1-10 polyplexes, but not AGMA1-5 proved to be an effective intracellular siRNA carrier, able to trigger gene silencing in Hela and PC3 cell lines without eliciting cytotoxic effects. AGMA1-10 knocked down AKT-1 expression upon transfection with an AKT-1 specific siRNA. The polyplex entry mechanism was investigated and was mediated by macropinocytosis. In conclusion, AGMA1 has potential as an efficient, non-toxic tool for the intracellular delivery of siRNA and warrants further investigation.
引用
收藏
页码：891 / 898
页数：8
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