PEGylation of Polypropylenimine Dendrimer with Alkylcarboxylate Chain Linkage to Improve DNA Delivery and Cytotoxicity.

Hashemi, Maryam; Ayatollahi, Sara; Parhiz, Hamideh; Mokhtarzadeh, Ahad; Javidi, Soheila; Ramezani, Mohammad

One of the major limitations of effective nonviral gene carriers is their potential high cytotoxicity. Conjugation of polyethylene glycol (PEG) to polymers is a common approach to decrease toxicity and improve biodistribution. The aim of this study was to evaluate the effect of PEGylation on generation 5 polypropylenimine (PPI) dendrimer by using PEG moieties or alkyl-PEG groups. Polymers were synthesized by grafting of 5 and 10 % primary amines of PPI to NH-PEG-COOH or Br-(CH)-CO-NH-PEG-COOH through Amide bond formation or nucleophilic substitution, respectively. Transfection efficiency and cytotoxicity were analyzed after 4 and 24 h exposure of neuroblastoma cell line (Neuro-2a) with synthesized vectors. Among all of the PEG-PPI derivatives, 5 % PEG-conjugated G5 PPI with alkyl chain (PPI-alkyl-PEG 5 %) resulted in the most efficient gene expression. This vector also significantly decreased the in vitro cytotoxicity and sub-G1 peak in flow cytometry histogram after 24 h incubation. Our results indicate that modification of 5 % primary amines of G5 PPI with PEG using alkyl chain as linker produces a promising vector combining low cytotoxicity, appropriate biodegradability, and high gene transfection efficiency.

DENDRIMERS; CELL-mediated cytotoxicity; GENE delivery techniques; POLYPROPYLENE; POLYPROPYLENE oxide

Applied Biochemistry & Biotechnology, 2015, Vol 177, Issue 1, p1

0273-2289

Academic Journal

10.1007/s12010-015-1723-y