Acta Pharmacologica Sinica (2010) 31: 509–514; doi: 10.1038/aps.2010.15

Acta Pharmacologica Sinica (2010) 31: 509–514; doi: 10.1038/aps.2010.15; published online 29 Mar 2010

Original Article

A novel polymer-lipid hybrid nanoparticle for efficient nonviral gene delivery

Jian LI¹, Ying-zi HE¹, Wen LI², Yun-zhen SHEN², Yu-ru LI^{3, *}, Yun-feng WANG^{2, *}

Institutes of Biomedical Sciences of Fudan University, Shanghai 200032, China; ²Department of Otolaryngology, Affiliated Eye and ENT Hospital of Fudan University, Shanghai 200031, China; ³Department of Otolaryngology, the First Hospital of Harbin Medical University, Harbin 150001, China

Aim: To develop a novel non-viral vector with high transfection efficiency and low cytotoxicity.

Methods: Poly (ethylene glycol)-distearoylphosphatidylethanolamine (PEG-DSPE) was incorporated into polymer-lipid hybrid nanoparticles (PLN) to construct a PEG-DSPE modified long circulating PLN (L-PLN). The L-PLN was prepared by the emulsifying-solvent evaporation method, L-PLN and L-PLN/DNA complexes were characterized. Both HEK293 and MDA-MB-231 cells transfected by L-PLN/DNA complexes were observed under a fluorescence microscope. The transfection efficiency of the complexes to HEK293 cells was further evaluated by flow cytometry.

Results: The GFP fluorescence intensity in HEK293 cells transfected by the L-PLN/DNA complexes (N/P=10) was about 37.2%, which was higher than those transfected by PLN alone or commercial Lipofectamine^TM 2000. The L-PLN exhibited minimal toxicity at a low N/P ratio compared with other vectors.

Conclusion: L-PLN as a novel gene delivery system, has higher transfection efficiency and acceptable cytotoxicity compared to the corresponding PLN, which is beneficial for the development of non-viral gene transfer vectors and may offer an alternative strategy for the future gene therapy.

Keywords: polymer-lipid hybrid nanoparticles; non-viral vectors; polyethylenimine; poly(ethylene glycol)-distearoylphosphatidylethanolamine; triolein; gene delivery

The work was supported by the National Basic Research of 973 Program (No 2006CB943701).

* To whom correspondence should be addressed.
E-mail wyf80612@gmail.com (Yun-feng WANG); yuruli612@gmail.com (Yu-ru LI)
Received 2009-11-02 Accepted 2010-01-20

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