Fourth Generation Phosphorus-Containing Dendrimers: Prospective Drug and Gene Delivery Carrier

Shcharbin, Dzmitry; Dzmitruk, Volha; Shakhbazau, Antos; Гончарова, Н. В.; Seviaryn, Ihar; Kosmacheva, S. M.; Потапнев, М. П.; Pedziwiatr-Werbicka, Elzbieta; Bryszewska, Maria; Talabaev, M.; Chernov, Alexander N.; Kulchitsky, Vladimir A.; Caminade, Anne‐Marie; Majoral, Jean‐Pierre

doi:10.3390/pharmaceutics3030458

Cited by 49 publications

(38 citation statements)

References 37 publications

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“…With regard to transfection studies, most widely investigated group of CPD is diethylamine-terminated dendrimers with cyclotriphosphazene core. They were successfully implemented as carriers of plasmids [13][14][15], oligodeoxynucleotides [14,16] and siRNAs [17]. Loup et al [13] highlighted better transfection efficiency of dendrimers of this group in the presence of serum than its absence during their plasmid transfection study.…”

Section: Introductionmentioning

confidence: 99%

Multi-Target Inhibition of Cancer Cell Growth by SiRNA Cocktails and 5-Fluorouracil Using Effective Piperidine-Terminated Phosphorus Dendrimers

Ihnatsyeu-Kachan

Dzmitruk

Apartsin

et al. 2017

Colloids and Interfaces

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Currently, RNAi based approaches for cancer treatment involving short double stranded RNA molecules (siRNA) are under vigorous scrutinization. Due to numerous biological obstacles, siRNA delivery into target cells requires protective escort. On the other hand, combining of siRNA-mediated gene silencing and action of conventional chemotherapeutics can propose additional enhancement of anticancer activity. In the present study, we investigated a siRNA cocktail able to downregulate anti-apoptotic genes (BCL-xL, BCL-2, MCL-1) and the chemotherapeutic agent 5-fluorouracil (5-FU) to evaluate multi-target cytotoxic effect on human cervical carcinoma cells (HeLa cell line). Novel phosphorus containing dendrimers of 3rd and 4th generations (namely AE2G3 and AE2G4) with voluminous piperidine terminal cationic groups were designed and tested as siRNA carriers. Dendrimers of both generations showed remarkable ability to bind pro-apoptotic siRNAs and provided 80-100% siRNA uptake by HeLa cells in the serum containing medium, while the widespread transfection agent Lipofectamine showed only~40% uptake. SiRNA cocktail (in low concentrations 50 and 100 nM) delivered by AE2G3 dendrimer caused almost complete elimination of cancer cells. We have discovered considerable increase of 5-FU cytotoxic effect by addition of AE2G3/siRNA cocktail complexes in low doses. Thus, we demonstrated the effectiveness of combined multi-target siRNA anticancer approach and described new highly effective serum stable nanomaterial vehicle for gene-based drugs.

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Section: Introductionmentioning

confidence: 99%

Multi-Target Inhibition of Cancer Cell Growth by SiRNA Cocktails and 5-Fluorouracil Using Effective Piperidine-Terminated Phosphorus Dendrimers

Ihnatsyeu-Kachan

Dzmitruk

Apartsin

et al. 2017

Colloids and Interfaces

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“…The breadth across applications is attributed to dendrimers being well-defined, monodisperse nanostructures with tunable critical nanoscale design parameters [15,16], such as size, shape, rigidity, surface functionality, and solvent affinity. For this reason, dendrimers have been studied as hosts for a number of guest species: drugs [1][2][3][4], gene [17][18][19], contrast agents [7,20,21], metal ions [9][10][11][12][13][14], polymers [22], and organic pollutants [23,24]. Astruc and coworkers have written an exceptionally comprehensive review on dendrimers functioning as hosts [25].…”

Section: Introductionmentioning

confidence: 99%

Multiscale Modeling for Host-Guest Chemistry of Dendrimers in Solution

Kim

Lamm

2012

Polymers

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Dendrimers have been widely used as nanostructured carriers for guest species in a variety of applications in medicine, catalysis, and environmental remediation. Theory and simulation methods are an important complement to experimental approaches that are designed to develop a fundamental understanding about how dendrimers interact with guest molecules. This review focuses on computational studies aimed at providing a better understanding of the relevant physicochemical parameters at play in the binding and release mechanisms between polyamidoamine (PAMAM) dendrimers and guest species. We highlight recent contributions that model supramolecular dendrimer-guest complexes over the temporal and spatial scales spanned by simulation methods ranging from all-atom molecular dynamics to statistical field theory. The role of solvent effects on dendrimer-guest interactions and the importance of relating model parameters across multiple scales is discussed.

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“…These first experiments have been extended to check the ability of the G 4 + dendrimer to interact with the fluorescent probe 8-anilino-1-naphthalenesulfonate (ANS), the antineoplasic drug cisplatin, and the anti-HIV siRNA siP24, and also to check its capability to deliver the green fluorescent protein gene (pGFP) into cells (Shcharbin et al, 2011). The usefulness of G 4 + to deliver specific siRNA against HIV-1 (siNEF) in PBMCs to interfere in HIV-1 replication was also assessed.…”

Section: Phosphorhydrazone Dendrimers En-ded By Ammonium Groupsmentioning

confidence: 99%

Biological properties of water-soluble phosphorhydrazone dendrimers

Caminade

Turrin

Majoral

2013

Braz. J. Pharm. Sci.

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1984-8250Dendrimers are hyperbranched and perfectly defined macromolecules, constituted of branches emanating from a central core in an iterative fashion. Phosphorhydrazone dendrimers constitute a special family of dendrimers, possessing one phosphorus atom at each branching point. The internal structure of these dendrimers is hydrophobic, but hydrophilic terminal groups can induce the solubility of the whole structure in water. Indeed, the properties of these compounds are mainly driven by the type of terminal groups their bear; this is especially true for the biological properties. For instance, positively charged terminal groups are efficient for transfection experiments, as drug carriers, as anti-prion agents, and as inhibitor of the aggregation of Alzheimer's peptides, whereas negatively charged dendrimers have anti-HIV properties and can influence the human immune system, leading to anti-inflammatory properties usable against rheumatoid arthritis. This review will give the most representative examples of the biological properties of water-soluble phosphorhydrazone dendrimers, organized depending on the type of terminal groups they bear

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Fourth Generation Phosphorus-Containing Dendrimers: Prospective Drug and Gene Delivery Carrier

Cited by 49 publications

References 37 publications

Multi-Target Inhibition of Cancer Cell Growth by SiRNA Cocktails and 5-Fluorouracil Using Effective Piperidine-Terminated Phosphorus Dendrimers

Multi-Target Inhibition of Cancer Cell Growth by SiRNA Cocktails and 5-Fluorouracil Using Effective Piperidine-Terminated Phosphorus Dendrimers

Multiscale Modeling for Host-Guest Chemistry of Dendrimers in Solution

Biological properties of water-soluble phosphorhydrazone dendrimers

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