Dataset Information

Sphingomyelin-Based Nanosystems (SNs) for the Development of Anticancer miRNA Therapeutics.

ABSTRACT: Gene replacement therapy with oncosuppressor microRNAs (miRNAs) is a promising alternative to interfere with cancer progression. However, miRNAs are highly inefficient in a biological environment, hampering a successful translation to clinics. Nanotechnology can tackle this drawback by providing delivery systems able to efficiently deliver them to cancer cells. Thus, the objective of this work was to develop biocompatible nanosystems based on sphingomyelin (SM) for the intracellular delivery of miRNAs to colorectal cancer cells. We pursued two different approaches to select the most appropriate composition for miRNA delivery. On the one hand, we prepared sphingomyelin-based nanosystems (SNs) that incorporate the cationic lipid stearylamine (ST) to support the association of miRNA by the establishment of electrostatic interactions (SNs-ST). On the other hand, the cationic surfactant (DOTAP) was used to preform lipidic complexes with miRNA (Lpx), which were further encapsulated into SNs (SNs-Lpx). Restitution of miRNA145 levels after transfection with SNs-Lpx was related to the strongest anticancer effect in terms of tumor proliferation, colony forming, and migration capacity assays. Altogether, our results suggest that SNs have the potential for miRNA delivery to develop innovative anticancer therapies.

SUBMITTER: Nagachinta S

PROVIDER: S-EPMC7076701 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Sphingomyelin-Based Nanosystems (SNs) for the Development of Anticancer miRNA Therapeutics.

Nagachinta Surasa S Bouzo Belen Lopez BL Vazquez-Rios Abi Judit AJ Lopez Rafael R Fuente Maria de la M

Pharmaceutics 20200222 2

Gene replacement therapy with oncosuppressor microRNAs (miRNAs) is a promising alternative to interfere with cancer progression. However, miRNAs are highly inefficient in a biological environment, hampering a successful translation to clinics. Nanotechnology can tackle this drawback by providing delivery systems able to efficiently deliver them to cancer cells. Thus, the objective of this work was to develop biocompatible nanosystems based on sphingomyelin (SM) for the intracellular delivery of ...[more]

PMID: 32098309

Similar Datasets

Project description:BACKGROUND:In silico experiments, with the aid of computer simulation, speed up the process of in vitro or in vivo experiments. Cancer therapy design is often based on signalling pathway. MicroRNAs (miRNA) are small non-coding RNA molecules. In several kinds of diseases, including cancer, hepatitis and cardiovascular diseases, they are often deregulated, acting as oncogenes or tumor suppressors. miRNA therapeutics is based on two main kinds of molecules injection: miRNA mimics, which consists of injection of molecules that mimic the targeted miRNA, and antagomiR, which consists of injection of molecules inhibiting the targeted miRNA. Nowadays, the research is focused on miRNA therapeutics. This paper addresses cancer related signalling pathways to investigate miRNA therapeutics. RESULTS:In order to prove our approach, we present two different case studies: non-small cell lung cancer and melanoma. KEGG signalling pathways are modelled by a digital circuit. A logic value of 1 is linked to the expression of the corresponding gene. A logic value of 0 is linked to the absence (not expressed) gene. All possible relationships provided by a signalling pathway are modelled by logic gates. Mutations, derived according to the literature, are introduced and modelled as well. The modelling approach and analysis are widely discussed within the paper. MiRNA therapeutics is investigated by the digital circuit analysis. The most effective miRNA and combination of miRNAs, in terms of reduction of pathogenic conditions, are obtained. A discussion of obtained results in comparison with literature data is provided. Results are confirmed by existing data. CONCLUSIONS:The proposed study is based on drug discovery and miRNA therapeutics and uses a digital circuit simulation of a cancer pathway. Using this simulation, the most effective combination of drugs and miRNAs for mutated cancer therapy design are obtained and these results were validated by the literature. The proposed modelling and analysis approach can be applied to each human disease, starting from the corresponding signalling pathway.

Dataset Information

Sphingomyelin-Based Nanosystems (SNs) for the Development of Anticancer miRNA Therapeutics.

Publications

Sphingomyelin-Based Nanosystems (SNs) for the Development of Anticancer miRNA Therapeutics.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets