Gene Delivery Efficacy of Polyethyleneimine-Introduced Chitosan Shell/Poly(methyl Methacrylate) Core Nanoparticles for Rat Mesenchymal Stem Cells

National Nanotechnology Center, Thailand Science Park, Paholyothin Rd., Pathumthani, 12120, Thailand.
Journal of Biomaterials Science Polymer Edition (Impact Factor: 1.65). 01/2010; 21(2):205-23. DOI: 10.1163/156856209X415503
Source: PubMed


This work investigated polyethyleneimine (PEI)-introduced chitosan (CS) (CS/PEI) nanoparticles as non-viral carrier of plasmid DNA for rat mesenchymal stem cells (MSCs). The CS/PEI nanoparticles were prepared by the emulsifier-free emulsion polymerization of methyl methacrylate monomer induced by a small amount of t-butyl hydroperxide in the presence of different concentrations of PEI mixed with CS. The resulting nanoparticles were characterized by their surface properties and buffering capacity. In vitro gene transfection was also evaluated. The introduction of PEI affected the surface charge, dispersing stability and buffering capacity of the nanoparticles. The CS/PEI nanoparticles formed a complex upon mixing with a plasmid DNA of luciferase. The complex enhanced the level of gene transfection and prolonged the time period of expression for MSCs, compared with those of plasmid DNA-original CS and PEI nanoparticles. Cytotoxicity of CS/PEI complexes with plasmid DNA was significantly low, depending on the amount of PEI introduced. It is concluded that the CS/PEI nanoparticle was a promising carrier for gene delivery of MSCs.

Full-text preview

Available from:
  • [Show abstract] [Hide abstract]
    ABSTRACT: It is expected that mesenchymal stem cells (MSCs) will be a cell source for cardiac reconstruction because of their differentiation potential and ability to supply growth factors. However, poor viability at the transplanted site often hinders the therapeutic potential of MSCs. Here, in a trial designed to address this problem, a non-viral carrier of cationized polysaccharide is introduced for genetic engineering of MSCs. Spermine-introduced dextran of cationized polysaccharide (spermine-dextran) was internalized into MSCs by way of a sugar-recognizable receptor to enhance the expression level of plasmid deoxyribonucleic acid (DNA). When genetically engineered by the spermine-dextran complex with plasmid DNA of adrenomedullin (AM), MSCs secreted a large amount of AM, an anti-apoptotic and angiogenic peptide. Transplantation of AM gene-engineered MSCs improved cardiac function after myocardial infarction significantly more than MSCs alone. Thus, this genetic engineering technology using the non-viral spermine-dextran is a promising strategy to improve MSC therapy for ischemic heart disease.
    Tissue Engineering 03/2007; 13(2):313-22. DOI:10.1089/ten.2006.0133 · 4.25 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The core-shell nanoparticles possessing poly(methyl methacrylate) (PMMA) core coated with chitosan (CS), polyethyleneimine (PEI), and chitosan-mixed-polyethyleneimine (CS/PEI) shells were synthesized in this work. The emulsifier-free emulsion polymerization triggered by a redox initiating system from t-butylhydroperoxide (TBHP) and amine groups on CS and/or PEI was used as a synthetic method. In the CS/PEI systems, the amount of CS was kept constant (0.5g), while the amount of PEI was varied from 0.1 to 0.5g. The surface and physico-chemical properties of prepared nanoparticles were then examined. FTIR spectra indicated the presence of grafted PMMA on CS and/or PEI, and the weight fraction of incorporated PEI in the CS/PEI nanoparticles. All nanoparticles were spherical in shape with uniform size distribution illustrated by scanning electron microscopy (SEM). The introduction of PEI to CS nanoparticles yielded the higher monomer conversion, grafting efficiency, and grafting percentage compared with the CS nanoparticles. The size of CS/PEI nanoparticles was smaller than the original CS and PEI nanoparticles, and tended to decrease with increasing amount of PEI introduced. The introduction of PEI also brought the higher colloidal stability to the nanoparticles as indicated by zeta-potential measurement and isoelectric point analysis. The nanoparticles exhibited a promising antibacterial activity against Staphylococcus aureus and Escherichia coli. The nanoparticle-bacteria interaction was studied via SEM. The results suggested that they would be useful as effective antibacterial agents.
    Colloids and surfaces B: Biointerfaces 02/2010; 77(2):219-26. DOI:10.1016/j.colsurfb.2010.01.029 · 4.15 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The targeting drug delivery systems (TDDS) have attracted extensive attention of researchers in recent years. More and more drug/gene targeted delivery carriers, such as liposome, magnetic nanoparticles, ligand-conjugated nanoparticles, microbubbles, etc., have been developed and under investigation for their application. However, the currently investigated drug/gene carriers have several disadvantages, which limit their future use in clinical practice. Therefore, design and development of novel drug/gene delivery vehicles has been a hot area of research. Recent studies have shown the ability of mesenchymal stem cells (MSCs) to migrate towards and engraft into the tumor sites, which make them a great hope for efficient targeted-delivery vehicles in cancer gene therapy. In this review article, we examine the promising of using mesenchymal stem cells as a targeted-delivery vehicle for cancer gene therapy, and summarize various challenges and concerns regarding these therapies.
    Journal of Controlled Release 10/2010; 147(2):154-62. DOI:10.1016/j.jconrel.2010.05.015 · 7.71 Impact Factor
Show more