Evaluation of Poly(amidoamine) Dendrimer Surface Modification with Poly(ethylene glycol) on Cytotoxicity Reduction

Objective: Generation ۵ poly (amidoamine) dendrimers are promising multipotent gene delivery vectors that provide favorable DNA condensation properties; however, their high toxicity limits their applications. Toxicity of PAMAM dendrimers depends on their type, generation and applied dosage in a way that lower generations (lower than G۵ dendrimers) and anionic dendrimers have lower toxicity than higher generations and cationic dendrimers. The aim of this study is to evaluate the effect of PEGylation on toxicity of G۵ PAMAM dendrimers. Methods: In this study, to improve their characteristics as gene delivery carriers, G۵ PAMAM dendrimers were conjugated to polyethylene glycol molecules (PEG, molecular weight ۳۵۰۰) at three different molar ratios of ۱۰, ۲۰ and ۳۰. Also the number of conjugated PEG chains was quantified using TNBSA and Ellman assays. The effect of different degrees of PEGylation on cytotoxicity and transfection efficiency of modified PAMAM dendrimers toward BT-۴۷۴ and MCF-۱۰A cell lines were assessed. Results: Compared to unconjugated, PEG conjugated PAMAM dendrimers had lower in vitro cytotoxicity, particularly at higher PEG to PAMAM molar ratios. Among all prepared PEG-PAMAM dendrimers, G۵ PAMAM dendrimers that conjugated to PEG at a molar ratio of ۱۰/۱ had the highest in vitro transfection rate in both cell lines. Conclusion: Our results showed that these PEG-conjugated PAMAM dendrimers possess a great potential for in vitro gene delivery.

کلیدواژه ها:

G۵ PAMAM dendrimers ، PEG conjugation ، Cytotoxicity ، دندریمرهای پلی آمیدو آمین نسل ۵ ، اتصال به پلی اتیلن گلیکول ، سمیت سلولی