Prevailingly cationic agmatine-based amphoteric polyamidoamine as a nontoxic, nonhemolytic, and "stealthlike" DNA complexing agent and transfection promoter.
AGMA1, a prevailingly cationic amphoteric polyamidoamine obtained by polyaddition of (4-aminobutyl)guanidine (agmatine) to 2,2-bis(acrylamido)acetic acid, was studied as a potential DNA carrier and transfection promoter. Fluorescein-labeled AGMA1 was prepared by conjugation with fluorescein isothiocyanate and its cell uptake, blood permanence, and body distribution studied. In spite of its cationic character, AGMA1 is neither toxic nor hemolytic in the pH range 4.0-7.4, circulates for a long time in the blood without preferentially localizing in the liver, easily enters HT-29 cells, gives stable complexes with DNA, and is endowed with good transfection efficiency, suggesting the ability to transport in the cytoplasm a DNA payload without any measurable membranolytic activity. If compared with other transfection promoters, including polyamidoamines of different structures, AGMA1 is apparently endowed with a unique combination of desirable requirements for a nonviral DNA polymer carrier and warrants potential as a transfection agent in vivo.
Ferruti
Paolo
P
Dipartimento di Chimica Organica e Industriale and Centro Interdisciplinare per i Materiali e le Interfacce Nanostrutturati, Università di Milano, via Venezian 21, 20133 Milano, Italy. paolo.ferruti@unimi.it
Franchini
Jacopo
J
Bencini
Marco
M
Ranucci
Elisabetta
E
Zara
Gian Paolo
GP
Serpe
Loredana
L
Primo
Luca
L
Cavalli
Roberta
R
D000376:Agmatine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D000818:Animals; D001692:Biological Transport; D002412:Cations / Q000737:chemistry; D002460:Cell Line; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D006461:Hemolysis; D006801:Humans; D011073:Polyamines / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity; D051381:Rats; D014162:Transfection
C521880:AGMA1 polymer; D002412:Cations; D011073:Polyamines; D000376:Agmatine; D004247:DNA; D016650:Fluorescein-5-isothiocyanate