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MicroRNAs are endogenous regulators of gene expression, deregulated in several cellular
diseases including cancer. Altering the cellular microenvironment by modulating the
microRNAs functions can regulate different genes involved in major cellular processes, and
this approach is now being investigated as a promising new generation of molecularly
targeted anti-cancer therapies. AntagomiRs (Antisense-miRNAs) are a novel class of
chemically modified stable oligonucleotides used for blocking the functions of endogenous
microRNAs, which are overexpressed. A key challenge in achieving effective microRNAbased
therapeutics lies in the development of an efficient delivery system capable of
specifically delivering antisense oligonucleotides and target cancer cells in living animals. We
are now developing an effective delivery system designed to selectively deliver antagomiR-
21 and antagomiR-10b to triple negative breast cancer cells, and to revert tumor cell
metastasis and invasiveness. The FDA-approved biodegradable PLGA-nanoparticles were selected as a carrier for antagomiRs delivery. Chemically modified antagomiRs (antagomiR-21 and antagomiR-10b) were co-encapsulated in PEGylated-PLGA-nanoparticles by using the double-emulsification (W/O/W) solvent evaporation method, and the resulting average particle size of 150-200nm was used for different in vitro and in vivo experiments. The antagomiR encapsulated PLGA-nanoparticles were evaluated for their in vitro antagomiRs delivery, intracellular release profile, and antagomiRs functional effects, by measuring the endogenous cellular targets, and the cell growth and metastasis. The xenografts of tumor cells in living mice were used for evaluating the anti-metastatic and anti-invasive properties of cells. The results showed that the use of PLGA for antagomiR delivery is not only efficient in crossing cell membrane, but can also maintain functional intracellular antagomiRs level for a extended period of time and achieve therapeutic effect in living animals.
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