Novel poly(amido amine)s with bioreducible disulfide linkages in their diamino-units: Structure effects and in vitro gene transfer properties

Piest, Martin; Lin, Chao; Mateos‐Timoneda, Miguel A.; Lok, M.C.; Hennink, Wim E.; Feijén, Jan; Engbersen, Johan F.J.

doi:10.1016/j.jconrel.2008.05.023

Cited by 82 publications

(81 citation statements)

References 39 publications

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“…Improved transfection activity of bioreducible polyplexes is an almost universal finding reported with various different types of bioreducible polycations, including polypeptides, polymethacrylates, and poly(amido amine)s (PAA) (Chen et al, 2006; Christensen et al, 2006; Lin et al, 2006; Manickam and Oupicky, 2006; Piest et al, 2008; You et al, 2007). The increased transfection activity is believed to be the consequence of the decreased affinity between DNA and the bioreducible polycations after their intracellular degradation.…”

Section: Introductionmentioning

confidence: 92%

Effect of cell membrane thiols and reduction-triggered disassembly on transfection activity of bioreducible polyplexes

Li¹,

Manickam²,

Chen³

et al. 2012

European Journal of Pharmaceutical Sciences

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Bioreducible polyplexes are promising vectors for delivery of nucleic acids due to low toxicity and favorable transfection activity. The often improved transfection is usually explained by enhanced intracellular reductive disassembly of the polyplexes. This study evaluated the effect of enhanced reductive disassembly on transfection activity of plasmid DNA and antisense oligonucleotide (AON) polyplexes based on a series of bioreducible poly(amido amine)s (PAA). We found that the presence of disulfide bonds in PAA had no effect on nucleic acid binding, hydrodynamic size and zeta potential of polyplexes. Increasing the disulfide content in PAA increased susceptibility to reduction-triggered DNA and AON release from the polyplexes. Increasing the disulfide content in PAA increased DNA transfection but had no effect on AON transfection. Plasma membrane protein thiols played a key role in the observed enhancement of DNA transfection. The presence of disulfide bonds in PAA had no significant effect on the rate of intracellular DNA clearance, suggesting that enhanced intracellular disassembly of the bioreducible polyplexes is not a major contributing factor to the improved transfection activity.

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Section: Introductionmentioning

confidence: 92%

Effect of cell membrane thiols and reduction-triggered disassembly on transfection activity of bioreducible polyplexes

Li¹,

Manickam²,

Chen³

et al. 2012

European Journal of Pharmaceutical Sciences

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“…It is notable that bioreducible p(CBA-AEP) polyplexes showed significant higher transfection efficiency than those from PAAs lacking the disulfide linkage in COS-7 cells, revealing that PAA polyplexes with appropriate disulfide content have highly improved biophysical properties, yielding enhanced transgene expression with low cytotoxicity. In another study, they explored a novel route to introduce disulfide moieties in linear PAAs by synthesizing the polymers via Michael addition of reducible amine monomer, N,N′-dimethylcystamine (DMC) with various bisacrylamides [49]. DMC-based SS-PAAs showed very high buffer capacities due to the position of the disulfide bond close to tertiary nitrogen atoms in the DMC, lowering the pKa value of these basic sites.…”

Section: Bioreducible Poly(amido Amine)smentioning

confidence: 99%

Bioreducible polymers for gene delivery

Kim

2011

Reactive and Functional Polymers

111

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Bioreducible polymers, which possess mainly disulfide linkages in the polymer structures, have appeared as ideal gene delivery carriers due to the high stability in extracellular physiological condition and bioreduction-triggered release of genetic materials, as well as decreased cytotoxicity because intracellular cytosol is a reducing environment containing high level of reducing molecules such as glutathione. This review will describe the initiation and recent advances in the development of bioreducible polymers for gene delivery, which includes reducibly cross-linked PEIs, polypeptides, polyion complex micelles, and poly(amido amine)s. There have been extensive researches performed to exhibit great gene delivery efficacy but still several important issues about pharmacokinetics or safety should be answered thoroughly for further rational design of bioreducible polymers having potentials in human gene delivery systems.

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“…The fits to the data correspond to the vesicle plus polymer model [Equation (1)(2)(3)(4)]. Table 3 summarizes the radius of gyration (R g ) of ISA23 measured in the presence of the different vesicle model membranes.…”

Section: Sans Characterizationmentioning

confidence: 99%

Interaction of an Endosomolytic Polyamidoamine ISA23 with Vesicles Mimicking Intracellular Membranes: A SANS/EPR Study

Griffiths

Nilmini

Carter

et al. 2010

Macromolecular Bioscience

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The mechanism of ISA23 · HCl interaction with model membrane vesicles (80-100 nm in diameter) was investigated using EPR in conjunction with SANS. For EPR, 16-DSE was dissolved in the vesicle membrane to measure its dynamics and polarity, whereas a spin-labeled (Tempo)-ISA 23 analogue was used to give a measure of the polymer flexibility. When ISA23 was added to the external vesicle surface, no interaction was found. This observation conflicts with the reported ability to lyse RBC, but is in agreement with recent studies that showed no effect on membrane permeability when a PAA was added to an incubation medium containing isolated lysosomal vesicles. The vesicle-mimetic models used here provide a new and useful tool for studying endosomolytic polymer/membrane interactions.

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Novel poly(amido amine)s with bioreducible disulfide linkages in their diamino-units: Structure effects and in vitro gene transfer properties

Cited by 82 publications

References 39 publications

Effect of cell membrane thiols and reduction-triggered disassembly on transfection activity of bioreducible polyplexes

Effect of cell membrane thiols and reduction-triggered disassembly on transfection activity of bioreducible polyplexes

Bioreducible polymers for gene delivery

Interaction of an Endosomolytic Polyamidoamine ISA23 with Vesicles Mimicking Intracellular Membranes: A SANS/EPR Study

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