Interactions of Poly(amidoamine) Dendrimers with Survanta Lung Surfactant: The Importance of Lipid Domains

Erickson, Blake; DiMaggio, Stassi; Mullen, Douglas G.; Kelly, Christopher V.; Leroueil, Pascale R.; Berry, Stephanie A.; Baker, James R.; Orr, Bradford G.; Holl, Mark M. Banaszak

doi:10.1021/la801497d

Cited by 37 publications

(47 citation statements)

References 29 publications

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“…5,18–24 Atomic force microscopy (AFM) experiments on supported lipid bilayers have provided evidence for both free and polymer-supported pores formed by cationic nanoparticles. 4,8,13,14,16,17 Although these studies provide a framework for understanding the cell membrane-cationic polymer interactions, the supported lipid bilayers have a much simpler lipid composition than living cell membranes. They are devoid of membrane proteins, cholesterol, and glycolipids.…”

Section: Introductionmentioning

confidence: 99%

Quantitative Measurement of Cationic Polymer Vector and Polymer–pDNA Polyplex Intercalation into the Cell Plasma Membrane

et al. 2015

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Cationic gene delivery agents (vectors) are important for delivering nucleotides, but are also responsible for cytotoxicity. Cationic polymers (L-PEI, jetPEI, and G5 PAMAM) at 1x to 100x the concentrations required for translational activity (protein expression) induced the same increase in plasma membrane current of HEK 293A cells (30-50 nA) as measured by whole cell patch-clamp. This indicates saturation of the cell membrane by the cationic polymers. The increased currents induced by the polymers are not reversible for over 15 minutes. Irreversibility on this time scale is consistent with a polymer-supported pore or carpet model and indicates that the cell is unable to clear the polymer from the membrane. For polyplexes, although the charge concentration was the same (at N: P ration of 10:1), G5 PAMAM and jetPEI polyplexes induced a much larger current increase (40- 50 nA) than L-PEI polyplexes (< 20 nA). Both free cationic lipid and lipid polyplexes induced a lower increase in current than cationic polymers (< 20 nA). To quantify the membrane bound material, partition constants were measured for both free vectors and polyplexes into the HEK 293A cell membrane using a dye influx assay. The partition constants of free vectors increased with charge density of the vectors. Polyplex partition constants did not show such a trend. The long lasting cell plasma permeability induced by exposure to the polymer vectors or the polyplexes provides a plausible mechanism for the toxicity and inflammatory response induced by exposure to these materials.

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Section: Introductionmentioning

confidence: 99%

Quantitative Measurement of Cationic Polymer Vector and Polymer–pDNA Polyplex Intercalation into the Cell Plasma Membrane

et al. 2015

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“…The interaction between cell membranes and nanocarriers, such as dendrimers, is very important, because in the most cases carriers have to get across the lipid bilayer without disrupting it. Previous studies based on atomic force microscopy (AFM) [12][13][14][15][16][17] isothermal titration calorimetry (ITC), fluorescence correlated spectroscopy (FCS) [17][18], in vitro experiments [13,[19][20] and molecular dynamics simulations (MD) [14,17,[21][22][23][24] showed that cationic dendrimers disrupt lipid bilayers by forming holes on the bilayer surface and may remove lipids from it. The degree of the disruption depends on the size and charge of the dendrimer.…”

Section: Introductionmentioning

confidence: 99%

A mechanistic view of lipid membrane disrupting effect of PAMAM dendrimers

Berényi

Mihály

Wacha

et al. 2014

Colloids and Surfaces B: Biointerfaces

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The effect of 5 th generation polyamidoamine (PAMAM G5) dendrimers on multilamellar dipalmitoylphosphocholine (DPPC) vesicles was investigated. PAMAM was added in two different concentration to the lipids (10 -3 and 10 -2 dendrimer/lipid molar ratios). The thermal behavior of the evolved systems was characterized by DSC; while the structure and the morphology were investigated with small-and wide-angel X-ray scattering (SWAXS), freeze-fracture electron microscopy (FFTEM) and phosphorus-31 nuclear magnetic resonance ( 31 P-NMR) spectroscopy, respectively. IR spectroscopy was used to study the molecular interactions between PAMAM and DPPC. The obtained results show that the dendrimers added in 10 -3 molar ratio to the lipids generate minor perturbations in the multilamellar structure and thermal character of liposomes, while added in 10 -2 molar ratio dendrimers cause major disturbance in the vesicular system. The terminal amino groups of the dendrimers are in strong interaction with the phosphate headgroups and through this binding dendrimers disrupt the regular multilamellar structure of DPPC. Besides highly swollen, fragmented bilayers, small vesicles are formed.

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“…Upon differences in cell types, the polyions can bind to the cellular compartments and accordingly induce compartmentalization within certain areas of the membranes and inadvertently trigger various signaling paths. Furthermore, nanoscaled defects were shown to be induced by PAMAM dendrimers through removing lipid from the fluid domains at a significantly greater rate than for the gel domains (Erickson et al, 2008). This reinforces a possibility of compartmentalization of synthetic polymers within different membrane domains as well as a differential effect of polymers on functional systems in the membranes that consecutively provoke inadvertent cytoplasmic/nucleic consequences directly and indirectly via secondary messengers such as G proteins.…”

Section: Cellular Trafficking and Toxicity Of Polycationic Nanostructmentioning

confidence: 57%

Toxicogenomics of Nonviral Cationic Gene Delivery Nanosystems

Omidi¹,

Kafil²,

Barar³

2011

Non-Viral Gene Therapy

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Interactions of Poly(amidoamine) Dendrimers with Survanta Lung Surfactant: The Importance of Lipid Domains

Cited by 37 publications

References 29 publications

Quantitative Measurement of Cationic Polymer Vector and Polymer–pDNA Polyplex Intercalation into the Cell Plasma Membrane

Quantitative Measurement of Cationic Polymer Vector and Polymer–pDNA Polyplex Intercalation into the Cell Plasma Membrane

A mechanistic view of lipid membrane disrupting effect of PAMAM dendrimers

Toxicogenomics of Nonviral Cationic Gene Delivery Nanosystems

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