Issue 5, 2010

Polyethyleneimine-grafted poly(N-3-hydroxypropyl)aspartamide as a biodegradable gene vector for efficient gene transfection

Abstract

A new biodegradable cationic copolymer, α,β-poly(N-3-hydroxypropyl)-DL-aspartamide (PHPA) grafted with polyethylenimine (PEI) was synthesized as a nonviral gene delivery vector by conjugating low molecular weight (LMW) PEI onto PHPA backbone. The polycation, termed PHPA-PEI, exhibited good ability to condense plasmid DNA (pDNA) into nanoparticles of around 150 nm with positive charge at a nitrogen/phosphorus (N/P) ratio of 15. The morphology of the nanoparticles observed by atomic force microscopy (AFM) was compact and spherical. PHPA-PEI also showed strong buffering capacity over the pH range 3–10 and protected well the condensed DNA from enzymatic degradation by DNase I over a period of time. pDNA release triggered by the synergistic effect of heparin and degradation demonstrated that PHPA-PEI formulation could continuously release the pDNA over a week. Transfection with pDNA pRL-CMV encoding Renilla luciferase reporter gene (Rluc), mediated by PHPA-PEI/pDNA complexes was carried out in 3T3, HEK293 and COS7 cell lines, and compared with that mediated by PEI (25 kDa)/pDNA complexes. The results showed that PHPA-PEI was not only superior in transfectivity to PEI (25 kDa) but also showed sustained high level luciferase expression. Furthermore, PHPA-PEI exhibited much lower cytotoxicity than PEI (25 kDa) in these cell lines. Therefore, PHPA-PEI may have great potential as a gene delivery vector with low cytotoxicity and high gene transfection efficiency for future gene therapy applications.

Graphical abstract: Polyethyleneimine-grafted poly(N-3-hydroxypropyl)aspartamide as a biodegradable gene vector for efficient gene transfection

Supplementary files

Article information

Article type
Paper
Submitted
11 Sep 2009
Accepted
20 Nov 2009
First published
06 Jan 2010

Soft Matter, 2010,6, 955-964

Polyethyleneimine-grafted poly(N-3-hydroxypropyl)aspartamide as a biodegradable gene vector for efficient gene transfection

D. Chen, Y. Ping, G. Tang and J. Li, Soft Matter, 2010, 6, 955 DOI: 10.1039/B918966A

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