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Fluorescent nanodiamonds as innovative delivery systems for MiR-34a replacement in breast cancer

M. Abate, A. Lombardi, A. Luce, M. Porru, C. Leonetti, M. Bocchetti, V. Campani, G. De Rosa, SF. Graziano, V. Nele, F. Cardile, FZ. Marino, R. Franco, A. Ronchi, M. Scrima, R. Sperlongano, R. Alfano, G. Misso, E. Amler, M. Caraglia, S. Zappavigna

. 2023 ; 33 (-) : 127-141. [pub] 20230619

Status not-indexed Language English Country United States

Document type Journal Article

Nanodiamonds are innovative nanocrystalline carbon particles able to deliver chemically conjugated miRNAs. In oncology, the use of miRNA-based therapies may represent an advantage, based on their ability to simultaneously target multiple intracellular oncogenic targets. Here, nanodiamonds were tested and optimized to deliver miR-34a, a miRNA playing a key role in inhibiting tumor development and progression in many cancers. The physical-chemical properties of nanodiamonds were investigated suggesting electrical stability and uniformity of structure and size. Moreover, we evaluated nanodiamond cytotoxicity on two breast cancer cell models and confirmed their excellent biocompatibility. Subsequently, nanodiamonds were conjugated with miR-34a, using the chemical crosslinker polyethyleneimine; real-time PCR analysis revealed a higher level of miR-34a in cancer cells treated with the different formulations of nanodiamonds than with commercial transfectant. A significant and early nanodiamond-miR-34a uptake was recorded by FACS and fluorescence microscopy analysis in MCF7 and MDA-MB-231 cells. Moreover, nanodiamond-miR-34a significantly inhibited both cell proliferation and migration. Finally, a remarkable anti-tumor effect of miR-34a-conjugated nanodiamonds was observed in both heterotopic and orthotopic murine xenograft models. In conclusion, this study provides a rationale for the development of new therapeutic strategies based on use of miR-34a delivered by nanodiamonds to improve the clinical treatment of neoplasms.

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$a Fluorescent nanodiamonds as innovative delivery systems for MiR-34a replacement in breast cancer / $c M. Abate, A. Lombardi, A. Luce, M. Porru, C. Leonetti, M. Bocchetti, V. Campani, G. De Rosa, SF. Graziano, V. Nele, F. Cardile, FZ. Marino, R. Franco, A. Ronchi, M. Scrima, R. Sperlongano, R. Alfano, G. Misso, E. Amler, M. Caraglia, S. Zappavigna
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$a Nanodiamonds are innovative nanocrystalline carbon particles able to deliver chemically conjugated miRNAs. In oncology, the use of miRNA-based therapies may represent an advantage, based on their ability to simultaneously target multiple intracellular oncogenic targets. Here, nanodiamonds were tested and optimized to deliver miR-34a, a miRNA playing a key role in inhibiting tumor development and progression in many cancers. The physical-chemical properties of nanodiamonds were investigated suggesting electrical stability and uniformity of structure and size. Moreover, we evaluated nanodiamond cytotoxicity on two breast cancer cell models and confirmed their excellent biocompatibility. Subsequently, nanodiamonds were conjugated with miR-34a, using the chemical crosslinker polyethyleneimine; real-time PCR analysis revealed a higher level of miR-34a in cancer cells treated with the different formulations of nanodiamonds than with commercial transfectant. A significant and early nanodiamond-miR-34a uptake was recorded by FACS and fluorescence microscopy analysis in MCF7 and MDA-MB-231 cells. Moreover, nanodiamond-miR-34a significantly inhibited both cell proliferation and migration. Finally, a remarkable anti-tumor effect of miR-34a-conjugated nanodiamonds was observed in both heterotopic and orthotopic murine xenograft models. In conclusion, this study provides a rationale for the development of new therapeutic strategies based on use of miR-34a delivered by nanodiamonds to improve the clinical treatment of neoplasms.
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$a Lombardi, Angela $u Department of Precision Medicine, University of Campania "Luigi Vanvitelli," Via L. De Crecchio 7, 80138 Naples, Italy
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$a Luce, Amalia $u Department of Precision Medicine, University of Campania "Luigi Vanvitelli," Via L. De Crecchio 7, 80138 Naples, Italy
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$a Porru, Manuela $u Translational Oncology Research Unit, IRCCS Regina Elena National Cancer Institute, E Chianesi 53, 00144 Rome, Italy
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$a Leonetti, Carlo $u Translational Oncology Research Unit, IRCCS Regina Elena National Cancer Institute, E Chianesi 53, 00144 Rome, Italy
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$a Bocchetti, Marco $u Department of Precision Medicine, University of Campania "Luigi Vanvitelli," Via L. De Crecchio 7, 80138 Naples, Italy $u Laboratory of Precision and Molecular Oncology, Biogem Scarl, Institute of Genetic Research, Contrada Camporeale, 83031 Ariano Irpino, Italy
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$a Campani, Virginia $u Department of Pharmacy, University of Naples Federico II, D. Montesano 49, 80131 Naples, Italy
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$a Marino, Federica Zito $u Department of Mental and Physical Health and Preventive Medicine, Pathology Unit, University of Campania "Luigi Vanvitelli," 80138 Naples, Italy
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$a Sperlongano, Rossella $u Department of Precision Medicine, University of Campania "Luigi Vanvitelli," Via L. De Crecchio 7, 80138 Naples, Italy
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$a Amler, Evzen $u Department of Precision Medicine, University of Campania "Luigi Vanvitelli," Via L. De Crecchio 7, 80138 Naples, Italy $u Institute of Biophysics, 2nd Faculty of Medicine, Charles University, V Uvalu 84, 15006 Prague, Czech Republic
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$a Caraglia, Michele $u Department of Precision Medicine, University of Campania "Luigi Vanvitelli," Via L. De Crecchio 7, 80138 Naples, Italy $u Laboratory of Precision and Molecular Oncology, Biogem Scarl, Institute of Genetic Research, Contrada Camporeale, 83031 Ariano Irpino, Italy
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