PEGylated DNA/transferrin–PEI complexes: reduced interaction with blood components, extended circulation in blood and potential for systemic gene delivery

Ogris, Manfred; Brunner, Sylvia; Schüller, Susanne; Kircheis, Ralf; Wagner, Ernst

doi:10.1038/sj.gt.3300900

Cited by 1,144 publications

(969 citation statements)

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“…PEG incorporated into DNA complexes of cationic polymers can reduce their surface charge [25,26,31,34], cytotoxicity [25,27,31] and interaction with blood components [25], as well as prevent aggregation through steric stabilization [25,26,[29][30][31]33,34]. Because of its ability to modulate the properties of complexes, PEG has been reported to enhance transfection when attached to polymer-DNA complexes directly [24,27,33,34] or simply added to transfection media containing lipoplexes [49].…”

Section: Transfection On Sams On Goldmentioning

confidence: 99%

“…Polyethylene glycol (PEG), which has the monomeric repeat unit [-CH 2 -CH 2 -O]-, is widely used in drug and gene delivery and has been incorporated into DNA complexes of several cationic polymers, including polymethacrylate [23], PEI [24][25][26][27][28][29][30][31][32], PLL [33][34][35] and poly(amidoamine)s [36]. PEG reduces the surface charge of the complexes [25,26,31,34], which in turn reduces cytotoxicity [25,27,31]. The shielding effect of PEG also reduces the interaction between the complex and blood components (plasma proteins and erythrocytes) [25], and can prolong circulation of the complexes in the blood stream [25,32].…”

Section: Introductionmentioning

confidence: 99%

“…PEG reduces the surface charge of the complexes [25,26,31,34], which in turn reduces cytotoxicity [25,27,31]. The shielding effect of PEG also reduces the interaction between the complex and blood components (plasma proteins and erythrocytes) [25], and can prolong circulation of the complexes in the blood stream [25,32]. Furthermore, polyethylene glycosylation (PEGylation) can prevent salt-induced aggregation through steric stabilization [25,26,[29][30][31]33,34].…”

Section: Introductionmentioning

confidence: 99%

“…The shielding effect of PEG also reduces the interaction between the complex and blood components (plasma proteins and erythrocytes) [25], and can prolong circulation of the complexes in the blood stream [25,32]. Furthermore, polyethylene glycosylation (PEGylation) can prevent salt-induced aggregation through steric stabilization [25,26,[29][30][31]33,34]. Additionally, PEG is often used as a spacer for targeting ligands since the shielding effect of PEG is able to decrease nonspecific interactions with negatively charged cellular membranes, which results in reduction of nonspecific cellular uptake [37].…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, PEG is often used as a spacer for targeting ligands since the shielding effect of PEG is able to decrease nonspecific interactions with negatively charged cellular membranes, which results in reduction of nonspecific cellular uptake [37]. While some PEGylation strategies have had no effect on transfection efficiency in vitro [25,31,33] or in vivo [25], or even enhanced transfection [27,34], others have reported that PEGylation resulted in poor transfection [28,29,32], presumably due to interference with complexation [36]. These effects due to PEGylation have been associated with the extent of PEGylation, which may shield the surface charge [24,26], thus reducing cell binding and transfection, or alternatively, induce membrane leakage, resulting in enhanced cytoplasmic release [33,34].…”

Section: Introductionmentioning

confidence: 99%

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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: Transfection On Sams On Goldmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

2008

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Polycation-based DNA complexes for tumor-targeted gene deliveryin vivo

et al. 1999

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Background Efficient and target‐specific in vivo gene delivery is a major challenge in gene therapy. Compared to cell culture application, in vivo gene delivery faces a variety of additional obstacles such as anatomical size constraints, interactions with biological fluids and extracellular matrix, and binding to a broad variety of non‐target cell types. Methods Polycation‐based vectors, including adenovirus‐enhanced transferrinfection (AVET) and transferrin‐polyethylenimine (Tf‐PEI), were tested for gene delivery into subcutaneously growing tumors after local and systemic application. DNA biodistribution and reporter gene expression was measured in the major organs and in the tumor. Results Gene transfer after intratumoral application was 10–100 fold more efficient with Tf‐PEI/DNA or AVET complexes in comparison to naked DNA. Targeted gene delivery into subcutaneously growing tumors after systemic application was achieved using electroneutral AVET complexes and sterically stabilized PEGylated Tf‐PEI/DNA complexes, whereas application of positively charged polycation/DNA complexes resulted in predominant gene expression in the lungs and was associated by considerable toxicity. Conclusion For systemic application, the physical and colloidal parameters of the transfection complexes, such as particle size, stability, and surface charge, determine DNA biodistribution, toxicity, and transfection efficacy. By controlling these parameters, DNA biodistribution and gene expression can be targeted to different organs. Copyright © 1999 John Wiley & Sons, Ltd.

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