Application of membrane-based dendrimer/DNA complexes for solid phase transfection in vitro and in vivo

Bielinska, Anna U.; Yen, Ann; Wu, Huai Liang; Zahos, Kathleen M; Sun, Ryan; Weiner, Norman; Baker, James R.; Roessler, Blake J.

doi:10.1016/s0142-9612(99)00229-x

Cited by 152 publications

(112 citation statements)

References 47 publications

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“…Poly(L-lysine) (PLL) and polyethylenimine (PEI), modified with biotin residues, were complexed with DNA and bound to a neutravidin substrate [7,8], resulting in 100-fold increased transgene expression from the immobilized complexes relative to bolus delivery of complexes [7]. Plasmid DNA or DNA complexed with cationic polymers or lipids can also interact with substrates through nonspecific mechanisms [10][11][12][13][14][15][16][17][18]. Polyplexes and lipoplexes nonspecifically immobilized to substrates enhanced the extent of transgene expression in both cell lines and primary human-derived cells, along with an increased cellular viability [13].…”

Section: Introductionmentioning

confidence: 99%

Surface polyethylene glycol enhances substrate-mediated gene delivery by nonspecifically immobilized complexes

2008

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Substrate-mediated gene delivery describes the immobilization of gene therapy vectors to a biomaterial, which enhances gene transfer by exposing adhered cells to elevated DNA concentrations within the local microenvironment. Surface chemistry has been shown to affect transfection by nonspecifically immobilized complexes using self-assembled monolayers (SAMs) of alkanethiols on gold. In this report, SAMs were again used to provide a controlled surface to investigate whether the presence of oligo(ethylene glycol) (EG) groups in a SAM could affect complex morphology and enhance transfection. EG groups were included at percentages that did not affect cell adhesion. Nonspecific complex immobilization to SAMs containing combinations of EG-and carboxylic acidterminated alkanethiols resulted in substantially greater transfection than surfaces containing no EG groups or SAMs composed of EG groups combined with other functional groups. Enhancement in transfection levels could not be attributed to complex binding densities or release profiles. Atomic force microscopy imaging of immobilized complexes revealed that EG groups within SAMs affected complex size and appearance and could indicate the ability of these surfaces to preserve complex morphology upon binding. The ability to control the morphology of the immobilized complexes and influence transfection levels through surface chemistry could be translated to scaffolds for gene delivery in tissue engineering and diagnostic applications.

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Section: Introductionmentioning

confidence: 99%

Surface polyethylene glycol enhances substrate-mediated gene delivery by nonspecifically immobilized complexes

2008

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“…Plasmid DNA or DNA complexed with cationic polymers or lipids can also interact with substrates through non-specific, non-covalent mechanisms [11][12][13][14][15], including hydrophobic, electrostatic, and van der Waals interactions. These interactions have been well-characterized for adsorption and release of proteins from polymeric systems [16,17].…”

Section: Introductionmentioning

confidence: 99%

Substrate-mediated delivery from self-assembled monolayers: Effect of surface ionization, hydrophilicity, and patterning

2005

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Gene transfer has many potential applications in basic and applied sciences. In vitro, DNA delivery can be enhanced by increasing the concentration of DNA in the cellular microenvironment through immobilization of DNA to a substrate that supports cell adhesion. Substrate-mediated delivery describes the immobilization of DNA, complexed with cationic lipids or polymers, to a biomaterial or substrate. As surface properties are critical to the efficiency of the surface delivery approach, selfassembled monolayers (SAMs) of alkanethiols on gold were used to correlate surface chemistry of the substrate to binding, release, and transfection of non-specifically immobilized complexes. Surface hydrophobicity and ionization were found to mediate both DNA complex immobilization and transfection, but had no effect on complex release. Additionally, SAMs were used in conjunction with soft lithographic techniques to imprint substrates with specific patterns, resulting in patterned DNA complex deposition and transfection, with transfection efficiencies in the patterns nearing 40%. Controlling the interactions between complexes and substrates, with the potential for patterned delivery, can be used to locally enhance or regulate gene transfer, with applications to tissue engineering scaffolds and transfected cell arrays.

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“…The fact that the DNA in polyplexes is presented to the cells very differently from naked DNA, with respect to electrical charge (positive) and molecular condensation (condensed), is believed to facilitate cell uptake of complexes by adsorptive endocytosis. 4 Polycations used in gene delivery such as polyethyleneimine (PEI), 11 poly(L-histidine)-graft-poly(L-lysine), 12 and polyamidoamine (PAMAM) starburst dendrimers, 13 are polyamines that are cationic under physiological conditions and are capable of spontaneously forming complexes with DNA after removal of small counterions from both cationic polymer and DNA (a thermodynamically favored step, which drives and stabilizes polyplex formation). Polymers such as PEI have a high density of cationic groups such as secondary and tertiary amines whose charge is pH-dependent so that they can act as endosomal buffering systems.…”

Section: Introductionmentioning

confidence: 99%

Novel dextran–spermine conjugates as transfecting agents: comparing water-soluble and micellar polymers

et al. 2004

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Recently, a novel cationic polymer, dextran-spermine (D-SPM) was developed for gene delivery. An efficient transfection was obtained using this polycation for a variety of genes and cell lines in serum-free or serum-poor medium. However, transfection using the water-soluble D-SPMbased polyplexes decreased with increasing serum concentration in cell culture in a concentration-dependent manner, reaching 95% inhibition at 50% serum in the cell growth medium. In order to overcome this obstacle, oleyl derivatives of D-SPM (which form micelles in aqueous phase) were synthesized at 1, 10, and 20 mol% of oleyl moiety to polymer e-NH 2 to form N-oleyl-D-SPM (ODS). Polyplexes based on ODS transfected well in medium containing 50% serum. Comparison with polyplexes based on well-established polymers (branched and linear polyethyleneimine) and with DOTAP/Cholesterol lipoplexes showed that regarding b-galactosidase transgene expression level and cytotoxicity in tissue culture, the D-SPM and ODS compare well with the above polyplexes and lipoplexes. Intracellular trafficking using FITC-labeled ODS and Rhodamine-labeled pGeneGrip plasmid cloned with hBMP2 monitored by confocal microscopy revealed that during the transfection process the fluorescent-labeled polymer concentrates in the Golgi apparatus and around the nucleus, while the cell cytoplasm was free of fluorescent particles, suggesting that the polyplexes move in the cell toward the nucleus by vesicular transport through the cytoplasm and not by a random diffusion. We found that the plasmids penetrate the cell nucleus without the polymer. Preliminary results in zebra fish and mice demonstrate the potential of ODS to serve as an efficient nonviral vector for in vivo transfection. Gene Therapy (2005) 12, 494-503.

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Application of membrane-based dendrimer/DNA complexes for solid phase transfection in vitro and in vivo

Cited by 152 publications

References 47 publications

Surface polyethylene glycol enhances substrate-mediated gene delivery by nonspecifically immobilized complexes

Surface polyethylene glycol enhances substrate-mediated gene delivery by nonspecifically immobilized complexes

Substrate-mediated delivery from self-assembled monolayers: Effect of surface ionization, hydrophilicity, and patterning

Novel dextran–spermine conjugates as transfecting agents: comparing water-soluble and micellar polymers

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