Syntheses of Polycationic Dendrimers on Lipophilic Peptide Core for Complexation and Transport of Oligonucleotides

Wimmer, Norbert; Marano, Robert J.; Kearns, Philip S.; Rakoczy, Elizabeth; Tóth, István

doi:10.1016/s0960-894x(02)00511-5

Cited by 52 publications

(34 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previously in our laboratories, we have sought to overcome both of these problems with the introduction of a dendrimer-mediated delivery system for ODN-1, an anti-VEGF sense oligonucleotide, initially in vitro and subsequently in vivo. 12,13 In this instance, the dendrimer under investigation provided the conjugated ODN-1 a high degree of protection against nucleases in addition to effecting efficient delivery to the target site. However, the effective time of this protection, and its comparison to other methods of improving longevity had not yet been fully explored.…”

Section: Discussionmentioning

confidence: 99%

“…More recently, we described the synthesis and use of lipophilic amino-acid dendrimers that enhanced the delivery of ODN-1 into the retinal tissue of rats. 12,13 In addition, the data from this earlier study suggested that the dendrimers served as a protective agent against the effects of nucleases while enabling ODN-1 to interact with its target site within the gene.…”

Section: Introductionmentioning

confidence: 88%

“…In addition to this, group 2 consisted of two subgroups of four rats, which were injected with either ODN-1 6-FAM (subgroup 2a) or a dendrimer plus ODN-1 6-FAM conjugate (subgroup 2b) into the vitreous of both eyes. The synthesis of the dendrimer used (dendrimer 4) has been previously described 13 and is shown in Figure 7. At 2 months post injection, 6-9 lesions were introduced to both eyes of five rats from subgroups 1a, b and c by laser photocoagulation.…”

Section: Experimental Designmentioning

confidence: 99%

See 2 more Smart Citations

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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 88%

Section: Experimental Designmentioning

confidence: 99%

See 1 more Smart Citation

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

View full text Add to dashboard Cite

show abstract

“…Studies done by Wimmer and co-workers showed promising results for enhancing dendrimer cellular uptake and efficiency by conjugating a lipophilic lipoamino acid tail to a lysine dendrimer, which eventually improved membrane partitioning [21]. The solubility caused by the lipophilic tail facilitated entry of a cationic dendrimer-DNA complex and inhibited production of the human vascular endothelial growth factors (VEGF) which showed a better transfection than the transfection agent GSV.…”

Section: Dendrimers and Their Characteristicsmentioning

confidence: 99%

Dendrimer Nanoparticles and Their Applications in Biomedicine

Paul

Shao

Burdon

et al. 2013

Nanomaterials in Drug Delivery, Imaging, and Tissue Engineering

View full text Add to dashboard Cite

Dendrimers are a class of macromolecular materials with a highly branched three-dimensional structure. Since its inception in 1978, the dendrimers have attracted much attention for their biomedical applications. Structurally, dendrimers can be divided into three components: the core, the interior and the shell. The stepwise growth technique gives rise to nearly monodisperse polymeric tree-like macromolecules, which are essential for biological applications, since the monodispersity is a key factor for generation of reproducible structure that allows evaluation of the biological activity relating to specific structures. In addition, the reactive functional groups on the exterior give provision to modify its outer surface so as to achieve multivalent effects, such as improved pharmacokinetics, combined drug delivery, site specific delivery of therapeutics using targeting molecules, reduced cytotoxicity and limited long-term side effects. This chapter presents a basic concept of this evolving technology and explores the unique features of this nanomaterial for successful future applications as biotherapeutics.

show abstract

“…For instance, Florence et al [19] reported cationic polymeric amphiphiles comprising dendritic poly(L-lysine)s with their dendritic cores bonded to various alkyl chains, and found that hydrophobicity and molar charge ratio were two key factors for producing compact and reproducible polyplexes. Toth et al [20] also found that a combination with dendritic poly(L-lysine) and linear hydrophobic peptide could lead to stable ODNA/vector polyplexes and optimal delivery efficacy in vitro and in vivo. Through conjugating alkyl groups to cationic peptide chains, Stupp et al [21] revealed the peptide amphiphiles could exhibit extremely high DNA binding affinities.…”

Section: Introductionmentioning

confidence: 99%

Amphiphilic Cationic [Dendritic poly(L‐lysine)]‐block‐poly(L‐lactide)‐block‐[dendritic poly(L‐lysine)]s in Aqueous Solution: Self‐Aggregation and Interaction with DNA as Gene Delivery Carriers

Zhu¹,

Sheng²,

Luo³

et al. 2010

Macromolecular Bioscience

View full text Add to dashboard Cite

A new series of triblock [dendritic poly(L-lysine)]-block-PLLA-block-[dendritic poly(L-lysine)]s (DL(2) -PLLA-DL(2) ) with PLLA block lengths of 11.5-26.5 and double 2-generation PLL dendrons DL(2) as model cationic amphiphiles were synthesized and characterized. Their CAC, self-aggregation and plasmid DNA binding affinities in pure water and PBS were studied. The PLLA block length dependence of particle size, morphology and ξ potential for organized pDNA/amphiphile polyplex aggregates were examined. Finally, toxicities of these DL(2) -PLLA-DL(2) amphiphiles and their polyplexes were assayed by MTT with HeLa, SMMC-7721 and COS-7 cells, and COS-7 cell luciferase and eGFP gene transfection efficacies with these amphiphiles as the delivery carriers were investigated.

show abstract

Syntheses of Polycationic Dendrimers on Lipophilic Peptide Core for Complexation and Transport of Oligonucleotides

Cited by 52 publications

References 15 publications

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

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

Dendrimer Nanoparticles and Their Applications in Biomedicine

Amphiphilic Cationic [Dendritic poly(L‐lysine)]‐block‐poly(L‐lactide)‐block‐[dendritic poly(L‐lysine)]s in Aqueous Solution: Self‐Aggregation and Interaction with DNA as Gene Delivery Carriers

Contact Info

Product

Resources

About