Polyethylenimine-grafted polycarbonates as biodegradable polycations for gene delivery

Wang, Chang-Fang; Lin, Yanxin; Jiang, Tao; He, Feng; Zhuo, Ren‐Xi

doi:10.1016/j.biomaterials.2009.05.053

Cited by 101 publications

(76 citation statements)

References 34 publications

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“…PEI with a high Mn (.10 kDa) has a high transfection efficiency, [37][38][39] whereas PEI with a low Mn (,5 kDa) has a low transfection efficiency. 39,40 For expression of the gene delivered, the gene has to escape from the endosome and be transferred into the nucleus. The high transfection efficiency of high molecular weight PEI is thought to be caused by facilitation of endosomal escape by the proton sponge effect.…”

Section: Discussionmentioning

confidence: 99%

Effect of molecular weight of polyethyleneimine on loading of CpG oligodeoxynucleotides onto flake-shell silica nanoparticles for enhanced TLR9-mediated induction of interferon-α

Manoharan¹,

Ji²,

Yamazaki³

et al. 2012

IJN

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Background Class B CpG oligodeoxynucleotides primarily interact with Toll-like receptor 9 (TLR9) in B cells and enhance the immune system through induction of various interleukins including interleukin-6 in these immune cells. Although free class B CpG oligodeoxynucleotides do not induce interferon (IFN)-α production, CpG oligodeoxynucleotide molecules have been reported to induce IFN-α when loaded onto nanoparticles. Here, we investigated the in vitro induction of IFN-α by a nanocarrier delivery system for class B CpG oligodeoxynucleotide molecules. Methods For improving the capacity to load CpG oligodeoxynucleotide molecules, flake-shell SiO 2 nanoparticles with a specific surface area approximately 83-fold higher than that of smooth-surfaced SiO 2 nanoparticles were prepared by coating SiO 2 nanoparticles with polyethyleneimine (PEI) of three different number-average molecular weights (Mns 600, 1800, and 10,000 Da). Results The capacity of the flake-shell SiO 2 nanoparticles to load CpG oligodeoxynucleotides was observed to be 5.8-fold to 6.7-fold higher than that of smooth-surfaced SiO 2 nanoparticles and was found to increase with an increase in the Mn of the PEI because the Mn contributed to the positive surface charge density of the nanoparticles. Further, the flake-shell SiO 2 nanoparticles showed much higher levels of IFN-α induction than the smooth-surfaced SiO 2 nanoparticles. The highest IFN-α induction potential was observed for CpG oligodeoxynucleotide molecules loaded onto flake-shell SiO 2 nanoparticles coated with PEI of Mn 600 Da, although the CpG oligodeoxynucleotide density was lower than that on flake-shell SiO 2 nanoparticles coated with PEI of Mns 1800 and 10,000 Da. Even with the same density of CpG oligodeoxynucleotides on flake-shell SiO 2 nanoparticles, PEI with an Mn of 600 Da caused a markedly higher level of IFN-α induction than that with Mns of 1800 Da and 10,000 Da. The higher TLR9-mediated IFN-α induction by CpG oligodeoxynucleotides on flake-shell SiO 2 nanoparticles coated with a PEI of Mn 600 Da is attributed to residence of the CpG oligodeoxynucleotide molecules in endolysosomes.

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Section: Discussionmentioning

confidence: 99%

Effect of molecular weight of polyethyleneimine on loading of CpG oligodeoxynucleotides onto flake-shell silica nanoparticles for enhanced TLR9-mediated induction of interferon-α

Manoharan¹,

Ji²,

Yamazaki³

et al. 2012

IJN

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“…These non-viral vectors are considered as alternatives to overcome the adverse effects of viral vectors. Among the various types of non-viral vectors, cationic polymers such as polylysine (PLL) [6,7], polyethylenimine (PEI) [8][9][10][11], polyamidoamine dendrimer (PAMAM) [12][13][14][15] and chitosan [16][17][18] have received a great deal of attention owing to their advantageous properties as compared with the viral and cationic liposome-based vectors. For examples, they are easy to prepare and to be chemically modified.…”

Section: Introductionmentioning

confidence: 99%

Polyethylenimine-Based Amphiphilic Core–Shell Nanoparticles: Study of Gene Delivery and Intracellular Trafficking

Siu

Leung

et al. 2012

Biointerphases

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Amphiphilic core–shell nanoparticle, which is composed of a hydrophobic core and a branched polyethylenimine (PEI) shell, has been designed and synthesized as a novel gene delivery nanocarrier. In our previous study, we demonstrated that the core–shell nanoparticle was not only able to efficiently complex with plasmid DNA (pDNA) and protect it against enzymatic degradation, but also three times less cytotoxic, and threefold more efficient in gene transfection than branched 25 kDa PEI. This paper reports our further studies in the following three aspects: (1) the ability of the PEI-based nanoparticles to deliver gene in various mammalian cell lines; (2) intracellular distributions of the nanoparticles and their pDNA complexes in HeLa cells; and (3) incorporation of nuclear targeting agent into the nanoparticle/pDNA complexes to enhance the nuclear targeting ability. The PEI-based nanoparticles were able to transfect both human and non-human cell lines and their transfection efficiencies were cell-dependent. Within our four tested cell lines (MCF-7, BEL 7404, C6 and CHO-K1), gene transfer using PEI-based core–shell nanoparticles displayed gene expression levels comparable to, or even better than, the commercial Lipofectamine™ 2000. Confocal laser scanning microscopy showed that the nanoparticles and their pDNA complexes were effectively internalized into the HeLa cells. The in vitro time series experiments illustrated that both the nanoparticle/pDNA complexes and PEI-based nanoparticles were distributed in the cytoplasmic region after transfection for 10 and 60 min, respectively. Nuclear localization was also observed in both samples after transfection for 20 and 60 min, respectively. Incorporation of the high mobility group box 1 (HMGB1) protein for nuclear targeting has also been demonstrated with a simple approach: electrostatic complexation between the PEI-based nanoparticles and HMGB1. In the in vitro transfection study in MCF-7 cells, the expression level of the firefly luciferase gene encoded by the pDNA increased remarkably by up to eightfold when the HMGB1 protein was incorporated into the nanoparticle/pDNA complexes. Our results demonstrate that the PEI-based core–shell nanoparticles are promising nanocarriers for gene delivery.

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“…The transfection efficiency of these crosslinked PEI is considerably high, with cytotoxicity being much lower than that of PEI 25,000. [11][12][13][14] Other strategies have included using linear chains to link PEI together, such as grafting PEI to a linear polymer backbone to give comb-shaped copolymers, [15][16][17] conjugating low molecular weight PEI to a biocompatible polymer core to form star-shaped copolymers, 18,19 and constructing supramolecular polymers with grafting of low molecular weight PEI. 20,21 Poly(styrene-co-maleic anhydride) (SMA), an amphiphilic macromolecule, is an intermediate polymer that can be conveniently converted to a functional polymer by reacting with a bioactive agent containing amino or hydroxyl groups via a ring-opening reaction between the active agent and the succinic anhydride unit.…”

Section: Introductionmentioning

confidence: 99%

Amphiphilic graft copolymer based on poly(styrene-co-maleic anhydride) with low molecular weight polyethylenimine for efficient gene delivery

Li¹

2012

IJN

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Background and methods: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. Results: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. Conclusion:This work highlights the promise of SP as a safe and efficient synthetic vector for DNA delivery.

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Polyethylenimine-grafted polycarbonates as biodegradable polycations for gene delivery

Cited by 101 publications

References 34 publications

Effect of molecular weight of polyethyleneimine on loading of CpG oligodeoxynucleotides onto flake-shell silica nanoparticles for enhanced TLR9-mediated induction of interferon-α

Effect of molecular weight of polyethyleneimine on loading of CpG oligodeoxynucleotides onto flake-shell silica nanoparticles for enhanced TLR9-mediated induction of interferon-α

Polyethylenimine-Based Amphiphilic Core–Shell Nanoparticles: Study of Gene Delivery and Intracellular Trafficking

Amphiphilic graft copolymer based on poly(styrene-co-maleic anhydride) with low molecular weight polyethylenimine for efficient gene delivery

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Polyethylenimine-grafted polycarbonates as biodegradable polycations for gene delivery

Cited by 101 publications

References 34 publications

Effect of molecular weight of polyethyleneimine on loading of CpG oligodeoxynucleotides onto flake-shell silica nanoparticles for enhanced TLR9-mediated induction of interferon-&alpha;

Effect of molecular weight of polyethyleneimine on loading of CpG oligodeoxynucleotides onto flake-shell silica nanoparticles for enhanced TLR9-mediated induction of interferon-&alpha;

Polyethylenimine-Based Amphiphilic Core–Shell Nanoparticles: Study of Gene Delivery and Intracellular Trafficking

Amphiphilic graft copolymer based on poly(styrene-co-maleic anhydride) with low molecular weight polyethylenimine for efficient gene delivery

Contact Info

Product

Resources

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Effect of molecular weight of polyethyleneimine on loading of CpG oligodeoxynucleotides onto flake-shell silica nanoparticles for enhanced TLR9-mediated induction of interferon-α

Effect of molecular weight of polyethyleneimine on loading of CpG oligodeoxynucleotides onto flake-shell silica nanoparticles for enhanced TLR9-mediated induction of interferon-α