Comparison of the endocytic properties of linear and branched PEIs, and cationic PAMAM dendrimers in B16f10 melanoma cells

Seib, F. Philipp; Jones, Arwyn Tomos; Duncan, Ruth

doi:10.1016/j.jconrel.2006.10.020

Cited by 178 publications

(187 citation statements)

References 34 publications

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“…This would presumably lead to a much higher intravesicle concentrations of ISA1 and the temperature-dependency of cell association was indicative of an active process. (It is noteworthy that previous studies with OGlabelled polymers have shown both stability of the conjugate (little or no OG release over a 2 h incubation) and minimal pH-or concentration-dependent OG fluorescence quenching [27].) Endocytic internalisation of ISA1-OG by B16F10 cells in vitro was confirmed visually by fluorescence microscopy (Fig.…”

Section: Discussionsupporting

confidence: 64%

Intracellular fate of bioresponsive poly(amidoamine)s in vitro and in vivo

Richardson

Pattrick

Lavignac

et al. 2010

Journal of Controlled Release

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Linear poly(amidoamine)s (PAAs) have been designed to exhibit minimal non-specific toxicity, display pHdependent membrane lysis and deliver genes and toxins in vitro. The aim of this study was to measure PAA cellular uptake using ISA1-OG (and as a reference ISA23-OG) in B16F10 cells in vitro and, by subcellular fractionation, quantitate intracellular trafficking of 125 I-labelled ISA1-tyr in liver cells after intravenous (i.v.) administration to rats. The effect of time after administration (0.5-3 h) and ISA1 dose (0.04-100 mg/kg) on trafficking, and vesicle permeabilisation (N-acetyl-b-D-glucosaminidase (NAG) release from an isolated vesicular fraction) were also studied. ISA1-OG displayed~60-fold greater B16F10 cell uptake than ISA23-OG. Passage of ISA1 along the liver cell endocytic pathway caused a transient decrease in vesicle buoyant density (also visible by TEM). Increasing ISA1 dose from 10 mg/kg to 100 mg/kg increased both radioactivity and NAG levels in the cytosolic fraction (5-10 fold) at 1 h. Moreover, internalised ISA1 provoked NAG release from an isolated vesicular fraction in a dose-dependent manner. These results provide direct evidence, for the first time, of PAA permeabilisation of endocytic vesicular membranes in vivo, and they have important implications for potential efficacy/toxicity of such polymeric vectors.

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Section: Discussionsupporting

confidence: 64%

Intracellular fate of bioresponsive poly(amidoamine)s in vitro and in vivo

Richardson

Pattrick

Lavignac

et al. 2010

Journal of Controlled Release

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“…Recently, Seib and co-workers (28) have shown that PAMAM dendrimers enter cells at relatively higher levels compared to other linear and hyperbranched polymers. When effect of generation was examined, fourth generation dendrimers showed a tenfold higher uptake than third generation dendrimer.…”

Section: Cytotoxicity and Cellular Uptake Studiesmentioning

confidence: 99%

Potential Oral Delivery of 7-Ethyl-10-Hydroxy-Camptothecin (SN-38) using Poly(amidoamine) Dendrimers

2008

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Purpose-To investigate potential application of poly(amidoamine) (PAMAM) dendrimers for improving the delivery of SN-38.Methods-Complexes of SN-38 with generation 4 amine terminated PAMAM dendrimers were synthesized with varying amounts of drug. Stability of the complexes as well as influence of complexation on permeability across and cellular uptake by Caco-2 cells was evaluated.Results-The complexes were stable at pH 7.4 and drug was released at pH 5. A tenfold increase in permeability and more than hundredfold increase in cellular uptake of the complexes with respect to free SN-38 was observed.Conclusions-Studies suggest that complexation with PAMAM dendrimers has the potential to improve the oral bioavailability of SN-38.

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“…9 The most common carriers known to overcome endosomal degradation include PAMAM dendrimer 10,11 , poly(L-histidine) [12][13][14][15][16] , polyethylenimine (PEI) [17][18][19] 23 The results indicated that PAMAM-DNA complexes at low pH are more loosely bound than those at neutral pH value. There are also considerable reported differences in the size and stability of complexes formed from double-strand versus single-strand genes, with the latter showing greater stability and smaller particle size under physiological (salt) conditions.…”

Section: Introductionmentioning

confidence: 99%

The effect of pH on PAMAM dendrimer–siRNA complexation — Endosomal considerations as determined by molecular dynamics simulation

Ouyang

Zhang

Parekh

et al. 2011

Biophysical Chemistry

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Intracellular degradation of genes, most notably within the endo-lysosomal compartment is considered a significant barrier to (non-viral) gene delivery in vivo. Previous reports based on in vitro studies claim that carriers possessing a mixture of 1º, 2º & 3º amines are able to buffer the acidic environment within the endosome, allowing for timely release of their contents, leading to higher transfection rates. In this report, we adopt an atomistic molecular dynamics (MD) simulation approach, comparing the complexation of 21-bp siRNA with lowgeneration polyamidoamine (PAMAM) dendrimers (G0 and G1) at both neutral and acidic pHs, the latter of which mimics the degradative environment within maturing 'lateendosomes'. Our simulations reveal that the time taken for the dendrimer-gene complex (dendriplex) to reach equilibrium is appreciably longer at low pH and this is accompanied by more compact packaging of the dendriplex, as compared to simulations performed at neutral pH. We also note higher calculated binding free energies of the dendriplex at low pH, indicating a higher dendrimer-gene affinity in comparison with neutral pH. These novel simulations provide a more detailed understanding of low molecular-weight polymer-siRNA behaviour, mimicking the endosomal environment and provide input of direct relevance to the "proton sponge theory", thereby advancing the rational design of non-viral gene delivery systems.

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Comparison of the endocytic properties of linear and branched PEIs, and cationic PAMAM dendrimers in B16f10 melanoma cells

Cited by 178 publications

References 34 publications

Intracellular fate of bioresponsive poly(amidoamine)s in vitro and in vivo

Intracellular fate of bioresponsive poly(amidoamine)s in vitro and in vivo

Potential Oral Delivery of 7-Ethyl-10-Hydroxy-Camptothecin (SN-38) using Poly(amidoamine) Dendrimers

The effect of pH on PAMAM dendrimer–siRNA complexation — Endosomal considerations as determined by molecular dynamics simulation

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