Dendrimeric poly(propylene-imines) as effective delivery agents for DNAzymes: Toxicity, in vitro transfection and in vivo delivery

Tack, Frederik; Maes, S.; Dekeyser, N.; Bruining, Monique J.; Elissen-Román, C.; Janicot, Michel; Janssen, Henk M.; Waal, Bas F. M. de; Fransen, Peter; Lou, Xianwen; Meijer, E. W.; Ariën, Albertina; Brewster, Marcus E.

doi:10.1016/j.jconrel.2006.09.031

Cited by 8 publications

(3 citation statements)

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“…Macromolecules regularly arranged in a three-dimensional branch format with structures consisting of a multifunctional central core molecule Synthetic Peptides (e.g. BH3) [39] DNAzymes [40][41][42][43][44] DNA [45] Outer branches provide a large number of functional groups on the surface as attachment sites for carrier molecules [46] Inner branches provide dendritic channels that entrap carrier molecules Able to host both hydrophobic and hydrophilic molecules [17] Enhances solubility of drugs [47] Have not been investigated for their potential effect relating to biocompatibility or therapy [48] due to lack of clinical studies May generate immune response…”

Section: Doxorubicin-chitosan Nanoparticlesmentioning

confidence: 99%

Review: doxorubicin delivery systems based on chitosan for cancer therapy

Tan¹,

Choong²,

Dass³

2009

j pharm pharmacol

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Objectives This review sheds insight into an increasingly popular polymer that has been widely explored as a potential drug delivery system. The abundant, biodegradable and biocompatible polysaccharide chitosan, with many other favourable properties, has been favoured as a drug delivery system for the purposes of encapsulating and delivery of doxorubicin with reduced side-effects. Key findings Doxorubicin is frequently used as a frontline chemotherapeutic agent against a variety of cancers. It has largely been able to demonstrate anti-tumour effects, though there are major shortfalls of doxorubicin, which include serious side-effects such as cardiomyopathy and myelosuppression, and also an ever-present danger of extravasation during drug administration. In view of this, drug delivery systems are currently being explored as alternative methods of drug delivery in a bid to more effectively direct doxorubicin to the specific lesion site and reduce its systemic side-effects. Liposomes and dendrimers have been tested as potential carriers for doxorubicin; however they are not the focus of this review. Summary Recent advancements in doxorubicin and chitosan technology have shown some preliminary though promising results for cancer therapy.

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Section: Doxorubicin-chitosan Nanoparticlesmentioning

confidence: 99%

Review: doxorubicin delivery systems based on chitosan for cancer therapy

Tan¹,

Choong²,

Dass³

2009

j pharm pharmacol

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“…single-stranded DNA expression vectors [184 -186]; and complexing deoxyribozymes with dendrimers [187,188]. Furthermore, for targeted delivery the free deoxyribozyme must be introduced directly to the area of interest, which is not always practical in clinical settings.…”

Section: Rna-cleaving Deoxyribozymes As In Vivo Therapeutic Agentsmentioning

confidence: 99%

Deoxyribozymes: useful DNA catalysts in vitro and in vivo

Baum

Silverman

2008

Cell. Mol. Life Sci.

166

129

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Deoxyribozymes (DNA enzymes; DNAzymes) are catalytic DNA sequences. Using the technique of in vitro selection, individual deoxyribozymes have been identified that catalyze RNA cleavage, RNA ligation, and a growing range of other chemical reactions. DNA enzymes have been used in vitro for applications such as biochemical RNA manipulation and analytical assays for metal ions, small organic compounds, oligonucleotides, and proteins. Deoxyribozymes have also been utilized as in vivo therapeutic agents to destroy specific mRNA targets. Although many conceptual and practical challenges remain to be addressed, deoxyribozymes have substantial promise to contribute meaningfully for applications both in vitro and in vivo.

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“…Foremost, the transporter needs to complex and condense the genetic material, protect it from nucleolytic degradation, enable cellular uptake, and nally release it from the endosomal pathway into the cytosol, where the RNAi machinery is located. 31 Although high molecular weight dendrimers like PAMAM (poly(amidoamine)), 7,32,33 PPI (poly(propylene imine)), [34][35][36] and PEI (poly(ethylenimine)) [37][38][39] can lead to high transfection efficiencies, they also exhibit problematic toxicity proles, 40 which can be partially attributed to their cellular accumulation aer gene delivery has taken place. 41 An alternative approach, mainly established and advanced by Florence, 42 Sanya, 43 Diederich, 44 and Smith, 45 was to modify low-molecular-weight, amine-functionalized dendritic arrays with hydrophobic portions to promote their self-assembly into supramolecular dendrimers ("pseudodendrimers").…”

Section: Introductionmentioning

confidence: 99%

Polyglycerol-based amphiphilic dendrons as potential siRNA carriers for in vivo applications

et al. 2014

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The development of nonviral synthetic vectors for clinical application of gene therapy using siRNA transfection technology is of particular importance for treatment of human diseases, which is yet an unsolved challenge. By employing a rational design approach, we have synthesized a set of well-defined, low-molecular-weight dendritic polyglycerol-based amphiphiles, which are decorated peripherally with the DAPMA (N,N-di-(3-aminopropyl)-N-(methyl)amine) moiety. The main differences that were introduced in the structural motif relate to dendron generation and the type of linker between the hydrophilic and hydrophobic segment. The synthesized amphiphiles were then characterized for their aggregation behaviour and further evaluated with respect to their siRNA transfection potential by comparing their physico-chemical and biological features. Our findings demonstrated that all four synthesized amphiphiles yielded high gene binding affinities. Furthermore, the ester-linked compounds (G1-Ester-DAPMA, G2-Ester-DAPMA) revealed noticeable gene silencing in vitro without affecting the cell viability in the tumor cell line 786-O. Remarkably, neither G1-Ester-DAPMA nor G2-Ester-DAPMA induced inflammatory side effects after systemic administration in vivo, which is noteworthy because such highly positively charged compounds are typically associated with toxicity concerns which in turn supports their prospective application for in vivo purposes. Therefore, we believe that these structures may serve as new promising alternatives for nonviral siRNA delivery systems and have great potential for further synthetic modifications.

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Dendrimeric poly(propylene-imines) as effective delivery agents for DNAzymes: Toxicity, in vitro transfection and in vivo delivery

Cited by 8 publications

References 0 publications

Review: doxorubicin delivery systems based on chitosan for cancer therapy

Review: doxorubicin delivery systems based on chitosan for cancer therapy

Deoxyribozymes: useful DNA catalysts in vitro and in vivo

Polyglycerol-based amphiphilic dendrons as potential siRNA carriers for in vivo applications

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