DNA transfection and transfected cell viability using amphipathic asymmetric dendrimers

Shah, Dipen S; Sakthivel, Thiagarajan; Tóth, István; Florence, Alexander T.; Wilderspin, Andy

doi:10.1016/s0378-5173(00)00534-2

Cited by 145 publications

(81 citation statements)

References 6 publications

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“…Numerous kinds of experiment have been carried out to prove the potential application of this type of new material in biochemical, medical, technical and industrial fields [9][10][11][12] . In last two decades lots of efforts have been made to design and synthesize biocompatible dendrimer with different monomers having variety of functionalities.…”

Section: Introductionmentioning

confidence: 99%

Structure of poly(propyl ether imine) dendrimer from fully atomistic molecular dynamics simulation and by small angle x-ray scattering

Jana

Jayamurugan

Ganapathy

et al. 2006

The Journal of Chemical Physics

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Abstract:We study the structure of carboxylic acid terminated neutral poly (propyl ether imine) (PETIM) dendrimer from generation 1 through 6 (G1-G6) in a good solvent (water) by fully atomistic molecular dynamics (MD) simulations. We determine as a function of generation such structural properties as: radius of gyration, shape tensor, asphericity, fractal dimension, monomer density distribution, and end-group distribution functions. The sizes obtained from the MD simulations have been validated by Small Angle X-Ray Scattering (SAXS) experiment on dendrimer of generation 2 to 4 (G2 -G4). A good agreement between the experimental and theoretical value of radius of gyration has been observed. We find a linear increase in radius of gyration with the generation. In contrast, R g scales as ~x N with the number of monomers. We find two distinct exponents depending on the generations: x = 0.47 for G1-G3 and x = 0.28 for G3-G6 which reveals their non-space filling nature. In comparison with the amine terminated PAMAM dendrimer, we find R g of G-th generation PETIM dendrimer is nearly equal to that of (G+1)-th generation of PAMAM dendrimer as observed by Maiti et. al. [Macromolecules, 38, 979 2005]. We find substantial back folding of the outer sub generations into the interior of the dendrimer. Due to their highly flexible nature of the repeating branch units, the shape of the PETIM dendrimer deviates significantly from the spherical shape and the molecules become more and more spherical as the generation increases. The interior of the dendrimer is quite open with internal cavities available for accommodating guest molecules suggesting using PETIM * For correspondence: maiti@physics.iisc.ernet.in (PKM) or jayaraman@orgchem.iisc.ernet.in (NJ)or asood@physics.iisc.ernet.in (AKS) 2 dendrimer for guest-host applications. We also give a quantitative measure of the number of water molecules present inside the dendrimer.3

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Section: Introductionmentioning

confidence: 99%

Structure of poly(propyl ether imine) dendrimer from fully atomistic molecular dynamics simulation and by small angle x-ray scattering

Jana

Jayamurugan

Ganapathy

et al. 2006

The Journal of Chemical Physics

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“…Other studies have shown dendrimers to possess toxic side effects both in vitro and in vivo at high doses, but the effects were minimized by optimizing the dose, chemistry and DNA:dendrimer ratio. [22][23][24] Although not yet tested in human trials, no inflammatory response to the injected dendrimer or to the dendrimer plus ODN-1 was observed in our study at any time using ophthalmological examination. In addition, further examination using immunohistochemistry could not detect an increase in the presence of macrophages, which are related to an inflammatory response mediated by toxicity.…”

Section: Discussionmentioning

confidence: 60%

Dendrimer delivery of an anti-VEGF oligonucleotide into the eye: a long-term study into inhibition of laser-induced CNV, distribution, uptake and toxicity

et al. 2005

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We have performed a long-term study into the use of a lipophilic amino-acid dendrimer to deliver an anti-vascular endothelial growth factor (VEGF) oligonucleotide (ODN-1) into the eyes of rats and inhibit laser-induced choroidal neovascularization (CNV). In addition, the uptake, distribution and retinal tolerance of the dendrimer plus oligonucleotide conjugates were examined. Analysis of fluorescein angiograms of laser photocoagulated eyes revealed that dendrimer plus ODN-1 significantly inhibited (Po0.05) the development of CNV for 4-6 months by up to 95% in the initial stages. Eyes similarly injected with ODN-1 alone showed no significant difference (P40.05) in mean severity score at 2 months (2.8670.09), 4 months (2.1570.17) or 6 months (2.770.12) compared to the vehicle-injected controls. Furthermore, we showed that intravitreally injected ODN-1 tagged with 6-fam was absorbed by a wide area of the retina and penetrated all of the retinal cell layers to the retinal pigment epithelium. Ophthalmological examinations indicated that the dendrimers plus ODN-1 conjugates were well tolerated in vivo, which was later confirmed using immunohistochemistry, which showed no observable increase in antigens associated with inflammation. We conclude that the use of such dendrimers may provide a viable mechanism for the delivery of therapeutic oligonucleotides for the treatment of angiogenic eye diseases. Gene Therapy (2005) 12, 1544-1550.

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“…The complexes of (R/εLys) 15 À(RAMA) 3 -amide were able to transfect BHK cells as well as COS cells. 51 PAMAM Dendrimers. Starburst polyamidoamine (PAMAM) dendrimers ( Figure 2) are spherical, highly ordered, dendritic polymers with positively charged primary amino groups on their surface at physiological pH.…”

Section: à20mentioning

confidence: 99%

Nucleic Acid Carriers Based on Precise Polymer Conjugates

Troiber

Wagner

2011

Bioconjugate Chem.

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Polymer polydispersity, random conjugation of functional groups, and poorly understood structure–activity relationships have constantly hampered progress in the development of nucleic acid carriers. This review focuses on the synthetic concepts for the generation of precise polymers, site-specific conjugation strategies, and multifunctional conjugates for nucleic acid transport. Dendrimers, defined peptide carriers, sequence-defined polyamidoamines assembled by solid-phase supported synthesis, and precise lipopeptides or lipopolymers have been characterized for pDNA and siRNA delivery. Conjugation techniques such as click chemistries and peptide ligation are available for conjugating polymers with functional transport elements such as targeting or shielding domains and for direct covalent modification of therapeutic nucleic acids in a site-specific mode.

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DNA transfection and transfected cell viability using amphipathic asymmetric dendrimers

Cited by 145 publications

References 6 publications

Structure of poly(propyl ether imine) dendrimer from fully atomistic molecular dynamics simulation and by small angle x-ray scattering

Structure of poly(propyl ether imine) dendrimer from fully atomistic molecular dynamics simulation and by small angle x-ray scattering

Dendrimer delivery of an anti-VEGF oligonucleotide into the eye: a long-term study into inhibition of laser-induced CNV, distribution, uptake and toxicity

Nucleic Acid Carriers Based on Precise Polymer Conjugates

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