miRNA-205 Nanoformulation Sensitizes Prostate Cancer Cells to Chemotherapy.
Prasanth Kumar Bhusetty NageshPallabita ChowdhuryElham HatamiVijaya K N BoyaVivek K KashyapSheema KhanBilal B HafeezSubhash C ChauhanMeena JaggiMurali M YallapuPublished in: Cancers (2018)
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.
Keyphrases
- cell proliferation
- long non coding rna
- long noncoding rna
- prostate cancer
- iron oxide
- cell cycle
- flow cytometry
- photodynamic therapy
- randomized controlled trial
- cancer therapy
- oxidative stress
- high resolution
- cell death
- pi k akt
- high throughput
- squamous cell carcinoma
- radiation therapy
- locally advanced
- working memory
- endoplasmic reticulum stress
- mass spectrometry
- radical prostatectomy
- young adults
- binding protein