The AGMA1 polyamidoamine mediates the efficient delivery of siRNA

Abstract

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.

Polyamidoamines: Versatile Bioactive Polymers with Potential for Biotechnological Applications

“…M n 7800 AGMA1/siRNA polyplexes induced Akt1 gene silencing in HeLa and PC3 cells. The transfection efficiency was comparable with that of commercial siRNA transfection promoters, as for instance JetPEIVR and OligofectamineVR [116].…”

Ultrasound-Responsive Nrf2-Targeting siRNA-Loaded Nanobubbles for Enhancing the Treatment of Melanoma

“…In addition, siRNA complexation with cationic polymers via electrostatic interactions has been largely studied [56][57][58]. However, this approach suffers from some limitations, such as the stability issue in biological fluids, low transfection efficiency, and toxicity problems [45,55,59].…”

Extra-Small Gold Nanospheres Decorated With a Thiol Functionalized Biodegradable and Biocompatible Linear Polyamidoamine as Nanovectors of Anticancer Molecules

“…PAAs were previously investigated as anticancer drug carriers (Lavignac et al, 2009). In particular, the PAA nicknamed AGMA1 can be used as a potential non-viral, non-toxic and efficient vector for the intracellular delivery of siRNA and DNA (Cavalli et al, 2010;Cavalli et al, 2017). Interestingly, AGMA1, containing tert-amine, carboxyl and guanidine groups, whose repeat unit is reminiscent of the arggly-asp (RGD) peptide motif (Franchini et al, 2006), a wellknown fibronectin sequence mediating cell attachment, can act as an excellent cell adhesion and proliferation substrate (Gualandi et al, 2016).…”