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miRNA-205 Nanoformulation Sensitizes Prostate Cancer Cells to Chemotherapy.

Cancers (2018-08-29)
Prashanth K B Nagesh, Pallabita Chowdhury, Elham Hatami, Vijaya K N Boya, Vivek K Kashyap, Sheema Khan, Bilal B Hafeez, Subhash C Chauhan, Meena Jaggi, Murali M Yallapu
ABSTRAKT

The therapeutic application of microRNA(s) in the field of cancer has generated significant attention in research. Previous studies have shown that miR-205 negatively regulates prostate cancer cell proliferation, metastasis, and drug resistance. However, the delivery of miR-205 is an unmet clinical need. Thus, the development of a viable nanoparticle platform to deliver miR-205 is highly sought. A novel magnetic nanoparticle (MNP)-based nanoplatform composed of an iron oxide core with poly(ethyleneimine)-poly(ethylene glycol) layer(s) was developed. An optimized nanoplatform composition was confirmed by examining the binding profiles of MNPs with miR-205 using agarose gel and fluorescence methods. The novel formulation was applied to prostate cancer cells for evaluating cellular uptake, miR-205 delivery, and anticancer, antimetastasis, and chemosensitization potentials against docetaxel treatment. The improved uptake and efficacy of formulations were studied with confocal imaging, flow cytometry, proliferation, clonogenicity, Western blot, q-RT-PCR, and chemosensitization assays. Our findings demonstrated that the miR-205 nanoplatform induces significant apoptosis and enhancing chemotherapeutic effects in prostate cancer cells. Overall, these study results provide a strong proof-of-concept for a novel nonviral-based nanoparticle protocol for effective microRNA delivery to prostate cancer cells.

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Sigma-Aldrich
Dimethyl sulfoxide, Hybri-Max, sterile-filtered, BioReagent, suitable for hybridoma, ≥99.7%
Sigma-Aldrich
Polyethylenimine, branched, average Mw ~25,000 by LS, average Mn ~10,000 by GPC, branched
Sigma-Aldrich
Polyethylenimine, linear, average Mn 5,000, PDI ≤1.3