NANODIAMONDS AS AN INNOVATIVE SYSTEM FOR INTRACELLULAR DELIVERY OF MIRNA-34A IN PROSTATIC CANCER THERAPY

1,2 Bitti Giuseppe
Co-authors:
2,4 Abate Marianna 3 Neuhöferová Eva 3 Kindermann Marek 3 Petráková Vladimíra 2 Boccellino Mariarosaria 2 Quagliuolo Lucio 4 Filova Eva 3 Veronika Benson 2 Caraglia Michele 4 Amler Evzen
Institutions:
1 Charles University, Second Faculty of Medicine, V Úvalu 84, 150 06 Prague 5, Czech Republic, EU
2 University of Campania “Luigi Vanvitelli“, Department of Biochemistry, Biophysics and General Patology, Via L. De Crecchio, 7 - 80138 – Napoli, Italy, EU
3 Institute of Microbiology, Czech Academy of Sciences, Vídeňská 1083, 142 20 Prague 4, Czech Republic, EU
4 Institute of Experimental Medicine, AS CR,Laboratory of Tissue Engineering, Videnska 1083, 142 20 Prague 4, Czech Republic, EU
Conference:
9th International Conference on Nanomaterials - Research & Application, Hotel Voronez I, Brno, Czech Republic, EU, October 18th - 20th 2017
Proceedings:
Proceedings 9th International Conference on Nanomaterials - Research & Application
Pages:
449-454
ISBN:
978-80-87294-81-9
ISSN:
2694-930X
Published:
8th March 2018
Proceedings of the conference were published in Web of Science and Scopus.
Metrics:
10 views / 3 downloads
Abstract

The microRNA(miRNA)-34a is an important regulator of tumor suppression. It controls the expression of several target proteins involved in cell cycle, differentiation and apoptosis, and antagonizes processes that are necessary for basic cancer cell viability as well as cancer stemness, metastasis, and chemoresistance. It is downregulated in numerous cancer types, including prostatic cancer, and inhibits malignant growth by repressing genes involved in various oncogenic signaling pathways. Given the anti-oncogenic activity of miR-34a, here we proved the substantial benefits of a new therapeutic concept based on nanotechnology delivery of miRNA mimics. In order to monitor the miRNA-34a replacement, we used a fluorescent nanodiamond particles (FND) system with linked miRNA-34a mimic, which was delivered to PC3 and DU145 prostatic cancer cell lines. We used functionalized nanodiamonds coated with polyethylenimine to transfer miRNA-34a into PC3 and DU145 prostatic cancer cell lines and we measured the zeta-potential of these complexes before using them for in vitro experiments. A replacement of miRNA-34 was observed by monitoring levels of miRNA-34 via real-time PCR. Moreover, our in vitro experiments demonstrated that miRNA-34a replacement, using this FND delivery system, decreased viability and induced apoptosis in prostatic cancer cell lines. Our findings suggest the replacement of oncosuppressor miRNA-34a provides an effective strategy for cancer therapy and the FND-based delivery systems seems to be an excellent strategy for a safe and effective targeting of the tumor.

Keywords: miR-34a, nanodiamonds, delivery, prostate cancer, apoptosis
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