Amphiphilic Core−Shell Nanoparticles with Poly(ethylenimine) Shells as Potential Gene Delivery Carriers

University of Akron, Akron, Ohio, United States
Bioconjugate Chemistry (Impact Factor: 4.51). 01/2005; 16(1):139-46. DOI: 10.1021/bc049895l
Source: PubMed


Spherical, well-defined core-shell nanoparticles that consist of poly(methyl methacrylate) (PMMA) cores and branched poly(ethylenimine) shells (PEI) were synthesized via a graft copolymerization of methyl methacrylate from branched PEI induced by a small amount of tert-butyl hydroperoxide. The PMMA-PEI core-shell nanoparticles were between 130 to170 nm in diameter and displayed zeta-potentials near +40 mV at pH 7 in 1 mM aqueous NaCl. Plasmid DNA (pDNA) was mixed with nanoparticles and formed complexes of approximately 120 nm in diameter and was highly monodispersed. The complexes were characterized with respect to their particle size, zeta-potential, surface morphology, and DNA integrity. The complexing ability of the nanoparticles was strongly dependent on the molecular weight of the PEI and the thickness of the PEI shells. The stability of the complexes was influenced by the loading ratio of the pDNA and the nanoparticles. The condensed pDNA in the complexes was significantly protected from enzymatic degradation by DNase I. Cytotoxity studies using MTT colorimetric assays suggested that the PMMA-PEI (25 kDa) core-shell nanoparticles were three times less toxic than the branched PEI (25 kDa). Their transfection efficiencies were also significantly higher. Thus, the PEI-based core-shell nanoparticles show considerable potential as carriers for gene delivery.

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    • "An efficient gene delivery system must be able to protect DNA from degradation by nucleases in serum and in the extracellular matrix.35 As shown in Figure 6, after incubation with DNase I, the naked DNA and the DNA in PEI 800-DNA complexes were all completely degraded, while the DNA in SP-DNA complexes or PEI 25,000-DNA complexes remained intact, indicating that both SP-DNA complexes and PEI 25,000-DNA complexes can effectively protect DNA from degradation by DNase I. Quantification of the intact DNA (ImageJ, NIH) revealed that 93.0% and 94.4% of the loaded DNA was recovered from the SP-DNA complexes and PEI 25,000-DNA complexes, respectively, indicating that the ability of SP to protect DNA from enzymatic cleavage is comparable with that of PEI 25,000. "
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    ABSTRACT: A new amphiphilic comb-shaped copolymer (SP) was synthesized by conjugating poly(styrene-co-maleic anhydride) with low molecular weight polyethyleneimine for gene delivery. Fourier transform infrared spectrum, (1)H nuclear magnetic resonance, and gel permeation chromatography were used to characterize the graft copolymer. The buffering capability of SP was similar to that of polyethyleneimine within the endosomal pH range. The copolymer could condense DNA effectively to form complexes with a positive charge (13-30 mV) and a small particle size (130-200 nm) at N/P ratios between 5 and 20, and protect DNA from degradation by DNase I. In addition, SP showed much lower cytotoxicity than polyethyleneimine 25,000. Importantly, the gene transfection activity and cellular uptake of SP-DNA complexes were all markedly higher than that of complexes of polyethyleneimine 25,000 and DNA in MCF-7 and MCF-7/ADR cell lines. This work highlights the promise of SP as a safe and efficient synthetic vector for DNA delivery.
    International Journal of Nanomedicine 09/2012; 7:4961-72. DOI:10.2147/IJN.S32069 · 4.38 Impact Factor
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    • "Polymeric NPs have an advantage over both liposomes and lipid reagents because of their ease of manipulation, control over DNA release profiles, and biological stability in vivo [7]. In addition, the properties of these NPs can be easily modified, for example, by addition of functional polymer groups to increase uptake or improve release of cargo genetic material [4] [5] [8]. One of the major drawbacks to gene encapsulation in synthetic polymers for delivery using bottom-up techniques is the incorporation of plasmid DNA (pDNA) into the particles during the synthesis phase. "
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    Journal of Nanomaterials 01/2011; 2011. DOI:10.1155/2011/952060 · 1.64 Impact Factor
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    • "Secondly, instead of mixing water-soluble polycations and DNA (or siRNA) to form complexes, which would result in the formation of uncontrollable large particles , micellar nanoparticles with positive charge allows nucleic acid loading post nanoparticles formation. This is believed to be favorable for the construction of size-controllable and monodispersed nucleic acid loaded nanoparticles, which may display unique advantage for in vivo applications [32]. In addition, such preparation method may be convenient for expansion to meet large quantity requirement for therapeutic applications. "
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