Anticancer siRNA cocktails as a novel tool to treat cancer cells. Part (A). Mechanisms of interaction

Йонов, Максим; Łaźniewska, Joanna; Dzmitruk, Volha; Halets, Inessa; Loznikova, Svetlana; Новопашина, Д. С.; Apartsin, Evgeny; Krasheninina, Olga; Venyaminova, Alya G.; Miłowska, Katarzyna; Nowacka, Olga; Gomez-Ramirez, Rafael; Mata, F. Javier de la; Majoral, Jean‐Pierre; Shcharbin, Dzmitry; Bryszewska, Maria

doi:10.1016/j.ijpharm.2015.03.024

Cited by 65 publications

(69 citation statements)

References 56 publications

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“…However, just limited data on their interactions with siRNA and efficiency of delivery are published [17,19,20]. The first example of cationic phosphorus dendrimers contained diethylamine groups on the periphery [13].…”

Section: Discussionmentioning

confidence: 99%

“…The siRNA binding profile of piperidine-terminated dendrimers differed from that of diethylamine-terminated CPD in gel electrophoresis studies [19,20]. Although they have comparable size and the same amount of positively charged groups, AE2 dendrimers of 3rd and 4th form stable dendriplexes at lesser dendrimer/siRNA molar ratios (≥1.5 for both generations) compared to the same generations of diethylamine-terminated CPD (≥6 for both generations).…”

Section: Discussionmentioning

confidence: 99%

“…An effective application of the cocktail of pro-apoptotic siRNAs (siBCL-2, siBCL-xL, siMCL-1) for inhibition of cancer cells viability was reported in previous studies [17,20]. Here, we report on novel cationic phosphorus containing dendrimers of 3rd and 4th generations grafted with piperidine groups on the periphery that were synthesized and tested as siRNA carriers for RNAi-based cancer gene therapy with a chemotherapeutic combination approach.…”

Section: Introductionmentioning

confidence: 91%

“…Two major studies concerning binding properties of CPD towards siRNAs involved diethylamine-terminated dendrimers and were focused on siRNA directed against BCR [19] and anti-apoptotic genes (MCL-1, BCL-xL and BCL-2) [20]. Both studies report stable complex formation between CPD and siRNAs, with complexes being positively charged and secondary structure of siRNA unaltered.…”

Section: Introductionmentioning

confidence: 99%

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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: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Self Cite

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“…siRNA was gently mixed with transfection reagent and incubated at room temperature for 30 min. Liposome mixtures were added on 96-well plates, which were then incubated in a CO 2 chamber at 37°C for 36 h. Further tests were performed to examine the status of cell apoptosis (Ionov et al, 2015).…”

Section: Western Blotmentioning

confidence: 99%

5-Fluorouracil induces apoptosis of colorectal cancer cells

Zhang

Zhou

et al. 2016

Genet. Mol. Res.

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ABSTRACT. 5-Fluorouracil (5-FU) is widely used in chemotherapy for treatment of colorectal cancer. Leucine-rich repeat-containing G protein-coupled receptor (LGR) is known to participate in the occurrence and development of breast cancer by regulating the rebirth of tumor vessels. This study aimed to explore the proliferation and apoptosis of HCT116 colorectal cancer cells treated with 5-FU and related molecular mechanisms. 5-FU (20 µg/mL) was used to treat cultured HCT116 cells. An MTT test, flow cytometry, and colony formation assays were used to examine the proliferation and apoptosis of HCT116 cells. Western blotting was applied to detect the expression of the LGR4 protein in HCT116 cells. Small interference RNA or over-expression techniques were used to manipulate LGR4 expression in HCT116 cells and describe the proliferation and apoptosis of HCT116 treated with 5-FU. A dosage of 20 µg/mL 5-FU resulted in a significant decrease in the proliferation and apoptosis of HCT116 cells and significantly decreased expression levels of LGR4. The specific gene silence or over-expression of LGR4 in HCT116 cells increased and decreased the levels of apoptosis in HCT116, respectively. 5-FU induces apoptosis of colorectal cancer cells and inhibits proliferation by suppressing LGR4 proteins.

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Non‐Viral Nucleic Acid Delivery System for RNA Therapeutics

Liu

Zhou

et al. 2023

Advanced Therapeutics

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Nucleic acid drugs can treat diseases caused by defective or abnormal genes. Herein, the mechanism of non‐viral vectors for nucleic acid drug delivery is described. This review introduce non‐viral vectors for nucleic acid drug delivery, including the nucleic acid‐carrier conjugate, proteins and peptides‐based nanoparticles, polysaccharides, and other biological macromolecules‐based nanoparticles consisting of lipid nanoparticles, synthetic polymers‐based nanoparticles, inorganic nanoparticles, and organic–inorganic hybrid nanoparticles. Finally, the challenges and prospects of non‐viral vectors for nucleic acid drug delivery are discussed.

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Anticancer siRNA cocktails as a novel tool to treat cancer cells. Part (A). Mechanisms of interaction

Cited by 65 publications

References 56 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

5-Fluorouracil induces apoptosis of colorectal cancer cells

Non‐Viral Nucleic Acid Delivery System for RNA Therapeutics

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