Synthesis and Characterization of Four-Arm Poly(ethylene glycol)-Based Gene Delivery Vehicles Coupled to Integrin and DNA-Binding Peptides

Moore, Nicole M.; Barbour, Tiffany R.; Sakiyama‐Elbert, Shelly E.

doi:10.1021/mp700072n

Cited by 31 publications

(22 citation statements)

References 32 publications

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“…A number of polymers were selected based on their ability to assist other forms of transfection. Poly-L-glutamic acid (LMA1), Poly-ethylene-glycol (LME1), and Polyvinylpyrrolidone (LMV1) were selected due to their ability to enhance gene delivery to muscle cells via electroporation in vivo using another BTX electroporation device by us (unpublished data) and others (38) (39) (40). Poloxamer 188 (LMP8), a member of the family of pluronic-block co-polymers (41), has shown some promise in lipofection (42) (43).…”

Section: Resultsmentioning

confidence: 99%

Competitive electroporation formulation for cell therapy

Flanagan

Gimble

et al. 2011

Cancer Gene Ther

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Established cell transfection via nucleofection relies on nucleofection buffers with unknown and proprietary makeup due to trade secrecy, inhibiting the possibility of using this otherwise effective method for developing cell therapy. We devised a three-step method for discovering an optimal formulation for the nucleofection of any cell-line. These steps include the selection of the best nucleofection program and known buffer type, selection of the best polymer for boosting the transfection efficiency of the best buffer, and the comparison with the optimal buffer from an established commercial vendor (Amaxa). Using this 3-step selection system, competitive nucleofection formulations were discovered for multiple cell lines, which are equal to or surpass the efficiency of the Amaxa nucleofector solution in a variety of cells and cell lines, including primary adipose stem cells, muscle cells, tumor cells, and immune cells. Through the use of scanning electron microscopy, we have revealed morphological changes, which predispose for the ability of these buffers to assist in transferring plasmid DNA into the nuclear space. Our formulation may greatly reduce the cost of electroporation study in laboratory and boosts the potential of application of electroporation-based cell therapies in clinical trials.

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Section: Resultsmentioning

confidence: 99%

Competitive electroporation formulation for cell therapy

Flanagan

Gimble

et al. 2011

Cancer Gene Ther

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“…(Fischer et al, 2003; Intra and Salem, 2008; Nimesh and Chandra, 2009; Swami et al, 2007). PEI can be modified to reduce toxicity and its free amine groups can be used to conjugate cell binding or targeting ligands (Beyerle et al, 2010; Biswal et al, 2010; Bonsted et al, 2008; Breunig et al, 2008; Diebold et al, 1999a; Kang et al, 2010; Kim et al, 2008; Merkel et al, 2009b; Moore et al, 2008; Ogris M, 1999; Patnaik et al, 2010; Petersen et al, 2002; Zintchenko et al, 2008a). …”

Section: Introductionmentioning

confidence: 99%

Synthesis and characterization of mannosylated pegylated polyethylenimine as a carrier for siRNA

Kim

Jiang

Jacobi

et al. 2012

International Journal of Pharmaceutics

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Regulation of gene expression using small interfering RNA (siRNA) is a promising strategy for research and treatment of numerous diseases. In this study, we develop and characterize a delivery system for siRNA composed of polyethylenimine (PEI), polyethylene glycol (PEG), and mannose (Man). Cationic PEI complexes and compacts siRNA, PEG forms a hydrophilic layer outside of the polyplex for steric stabilization, and mannose serves as a cell binding ligand for macrophages. The PEI-PEG-mannose delivery system was constructed in two different ways. In the first approach, mannose and PEG chains are directly conjugated to the PEI backbone. In the second approach, mannose is conjugated to one end of the PEG chain and the other end of the PEG chain is conjugated to the PEI backbone. The PEI-PEG-mannose delivery systems were synthesized with 3.45 – 13.3 PEG chains and 4.7 – 3.0 mannose molecules per PEI. The PEI-PEG-Man-siRNA polyplexes displayed a coarse surface in Scanning Electron Microscopy (SEM) images. Polyplex sizes were found to range from 169nm to 357nm. Gel retardation assays showed that the PEI-PEG-mannose polymers are able to efficiently complex with siRNA at low N/P ratios. Confocal microscope images showed that the PEI-PEG-Man-siRNA polyplexes could enter cells and localized in the lysosomes at 2 hours post-incubation. Pegylation of the PEI reduced toxicity without any adverse reduction in knockdown efficiency relative to PEI alone. Mannosylation of the PEI-PEG could be carried out without any significant reduction in knockdown efficiency relative to PEI alone. Conjugating mannose to PEI via the PEG spacer generated superior toxicity and gene knockdown activity relative to conjugating mannose and PEG directly onto the PEI backbone.

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“…However, the strategy employed in this study is based on passive targeting, and the tumor with less leaky vasculature might get poor tumor retention. Previously, targeted PEI derivatives have been successfully constructed by conjugation with RGD peptides or various antibodies [3,[21][22][23][24][25][26]. With these targeting units, it is highly possible that the tumor uptake might be further improved due to specific targeting effect.…”

Section: Discussionmentioning

confidence: 99%