Efficacy and toxicity of linear polyamidoamine polymers used in gene deliveryTools Almulathanon, Ammar (2018) Efficacy and toxicity of linear polyamidoamine polymers used in gene delivery. PhD thesis, University of Nottingham.
AbstractIntroduction: Interestingly, polyamidoamines (PAAs) are a group of biodegradable cationic polymers that exhibit a transfection efficiency comparable to that obtained with PEI but with a low cytotoxicity compared to other polycationic vectors. However, their cellular adverse effects have only been probed in assays indirectly measuring the cell metabolic activity based on the reduction of tetrazolium salts into coloured formazan derivatives by mitochondrial enzymes such as the MTT, MTS or XTT assays. There is therefore a need for a deeper insight into their cytotoxic profile before their potential as delivery agents in gene therapy can be fully appreciated. Furthermore, the intracellular fate of PAA polyplexes remains unclear to date, prompting questions around the mechanisms underlying their ability to mediate gene transfer. The present work explored cellular events induced by DNA polyplexes prepared using a linear PAA with a methylenebisacrylamide/dimethylethylenediamine (MBA-DMEDA) backbone of a molecular weight over 10kDa with the aim to confirm and better understand the absence of relationship between cytotoxicity and transfection efficiency reported with those vectors.
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