Folic acid conjugated mPEG-PEI600 as an efficient non-viral vector for targeted nucleic acid delivery

Zhenhua Xu, Jiefu Jin, Leo K.S. Siu, Hong Yao, Johnny Sze, Hongzhe Sun, Hsiang Fu Kung, Wai Sang Poon, Samuel S.M. Ng, Marie C. Lin

Research output: Contribution to journalArticle

Abstract

In this study we describe a novel polymer, mPPS-FA, synthesized as a potential gene transfer vector. To complete mPPS-FA, folic acid was conjugated to a backbone (named mPPS) consisting of a copolymer of methyl PEG-2000, PEI-600, and sebacoyl chloride. 1H NMR, FT-IR, and UV spectroscopy were used to characterize the structure of mPPS-FA. It was revealed that mPPS-FA holds the ability to bind plasmid DNA yielding positively charged particles (polyplexes). Dynamic light scattering (DLS) and TEM techniques were used to study the size and morphology of the formed mPPS-FA/DNA nanocomplexes. The mPPS-FA/DNA nanoparticles exhibited low cytotoxicity as transfection of B16-F0, U87MG, CHO-1, and Ho-8910 cells produced >80% viability indicating low cytotoxicity of the polymer. The ability of mPPS-FA to deliver EGFP plasmid to melanoma B16-F0, U87, CHO-1, Ho-8910, and A549 cells was investigated in vitro as compared to the lipid-based transfection agent Lipofectamine™2000 and Linear PEI 22kDa (L-PEI 22kDa). We found that mPPS-FA/DNA complexes yielded the highest GFP transfection efficiency in B16-F0, U87, CHO-1, and Ho-8910 cells, which all highly express folate receptors (FR), at an mPPS-FA/DNA ratio (w/w) of 15. Furthermore, the transfection of mPPS-FA/DNA complexes in CHO-1 cells could be competitively blocked by free folic acid molecules. In contrast, in low FR expressing A549 cells, mPPS-FA showed similar low transfection efficiency as mPPS. Taken together, mPPS-FA showed the highest efficiency in vitro and the potential to be developed as a nonviral gene carrier.

Original languageEnglish (US)
Pages (from-to)182-192
Number of pages11
JournalInternational Journal of Pharmaceutics
Volume426
Issue number1-2
DOIs
StatePublished - Apr 15 2012

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Keywords

  • PEG
  • Polyethylenimine
  • Polymer
  • Tumor gene delivery

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Xu, Z., Jin, J., Siu, L. K. S., Yao, H., Sze, J., Sun, H., Kung, H. F., Poon, W. S., Ng, S. S. M., & Lin, M. C. (2012). Folic acid conjugated mPEG-PEI600 as an efficient non-viral vector for targeted nucleic acid delivery. International Journal of Pharmaceutics, 426(1-2), 182-192. https://doi.org/10.1016/j.ijpharm.2012.01.009