Fluorescent nanodiamonds as innovative delivery systems for MiR-34a replacement in breast cancer
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 teste...
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-09-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253123001622 |
| _version_ | 1827911205592760320 |
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| author | Marianna Abate Angela Lombardi Amalia Luce Manuela Porru Carlo Leonetti Marco Bocchetti Virginia Campani Giuseppe De Rosa Sossio Fabio Graziano Valeria Nele Francesco Cardile Federica Zito Marino Renato Franco Andrea Ronchi Marianna Scrima Rossella Sperlongano Roberto Alfano Gabriella Misso Evzen Amler Michele Caraglia Silvia Zappavigna |
| author_facet | Marianna Abate Angela Lombardi Amalia Luce Manuela Porru Carlo Leonetti Marco Bocchetti Virginia Campani Giuseppe De Rosa Sossio Fabio Graziano Valeria Nele Francesco Cardile Federica Zito Marino Renato Franco Andrea Ronchi Marianna Scrima Rossella Sperlongano Roberto Alfano Gabriella Misso Evzen Amler Michele Caraglia Silvia Zappavigna |
| author_sort | Marianna Abate |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T01:59:40Z |
| format | Article |
| id | doaj.art-c25edbbf2a774f64bb6dcb2905b5ccfc |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-03-13T01:59:40Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-c25edbbf2a774f64bb6dcb2905b5ccfc2023-07-02T04:16:36ZengElsevierMolecular Therapy: Nucleic Acids2162-25312023-09-0133127141Fluorescent nanodiamonds as innovative delivery systems for MiR-34a replacement in breast cancerMarianna Abate0Angela Lombardi1Amalia Luce2Manuela Porru3Carlo Leonetti4Marco Bocchetti5Virginia Campani6Giuseppe De Rosa7Sossio Fabio Graziano8Valeria Nele9Francesco Cardile10Federica Zito Marino11Renato Franco12Andrea Ronchi13Marianna Scrima14Rossella Sperlongano15Roberto Alfano16Gabriella Misso17Evzen Amler18Michele Caraglia19Silvia Zappavigna20Department of Precision Medicine, University of Campania “Luigi Vanvitelli,” Via L. De Crecchio 7, 80138 Naples, Italy; Institute of Biophysics, 2nd Faculty of Medicine, Charles University, V Uvalu 84, 15006 Prague, Czech RepublicDepartment of Precision Medicine, University of Campania “Luigi Vanvitelli,” Via L. De Crecchio 7, 80138 Naples, ItalyDepartment of Precision Medicine, University of Campania “Luigi Vanvitelli,” Via L. De Crecchio 7, 80138 Naples, ItalyTranslational Oncology Research Unit, IRCCS Regina Elena National Cancer Institute, E Chianesi 53, 00144 Rome, ItalyTranslational Oncology Research Unit, IRCCS Regina Elena National Cancer Institute, E Chianesi 53, 00144 Rome, ItalyDepartment of Precision Medicine, University of Campania “Luigi Vanvitelli,” Via L. De Crecchio 7, 80138 Naples, Italy; Laboratory of Precision and Molecular Oncology, Biogem Scarl, Institute of Genetic Research, Contrada Camporeale, 83031 Ariano Irpino, ItalyDepartment of Pharmacy, University of Naples Federico II, D. Montesano 49, 80131 Naples, ItalyDepartment of Pharmacy, University of Naples Federico II, D. Montesano 49, 80131 Naples, ItalyDepartment of Pharmacy, University of Naples Federico II, D. Montesano 49, 80131 Naples, ItalyDepartment of Pharmacy, University of Naples Federico II, D. Montesano 49, 80131 Naples, ItalyLaboratory of Precision and Molecular Oncology, Biogem Scarl, Institute of Genetic Research, Contrada Camporeale, 83031 Ariano Irpino, ItalyDepartment of Mental and Physical Health and Preventive Medicine, Pathology Unit, University of Campania “Luigi Vanvitelli,” 80138 Naples, ItalyDepartment of Mental and Physical Health and Preventive Medicine, Pathology Unit, University of Campania “Luigi Vanvitelli,” 80138 Naples, ItalyDepartment of Mental and Physical Health and Preventive Medicine, Pathology Unit, University of Campania “Luigi Vanvitelli,” 80138 Naples, ItalyLaboratory of Precision and Molecular Oncology, Biogem Scarl, Institute of Genetic Research, Contrada Camporeale, 83031 Ariano Irpino, ItalyDepartment of Precision Medicine, University of Campania “Luigi Vanvitelli,” Via L. De Crecchio 7, 80138 Naples, ItalyDepartment of Advanced Medical and Surgical Sciences “DAMSS,” University of Campania “Luigi Vanvitelli,” Via S. M. di Costantinopoli 104, 80138 Naples, ItalyDepartment of Precision Medicine, University of Campania “Luigi Vanvitelli,” Via L. De Crecchio 7, 80138 Naples, ItalyDepartment of Precision Medicine, University of Campania “Luigi Vanvitelli,” Via L. De Crecchio 7, 80138 Naples, Italy; Institute of Biophysics, 2nd Faculty of Medicine, Charles University, V Uvalu 84, 15006 Prague, Czech RepublicDepartment of Precision Medicine, University of Campania “Luigi Vanvitelli,” Via L. De Crecchio 7, 80138 Naples, Italy; Laboratory of Precision and Molecular Oncology, Biogem Scarl, Institute of Genetic Research, Contrada Camporeale, 83031 Ariano Irpino, Italy; Corresponding author: Prof. Michele Caraglia, Department of Precision Medicine, University of Campania “Luigi Vanvitelli,” Via L. De Crecchio 7, 80138 Naples, Italy.Department of Precision Medicine, University of Campania “Luigi Vanvitelli,” Via L. De Crecchio 7, 80138 Naples, Italy; Corresponding author: Prof. Silvia Zappavigna, Department of Precision Medicine, University of Campania “Luigi Vanvitelli,” Via L. De Crecchio 7, 80138 Naples, Italy.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.http://www.sciencedirect.com/science/article/pii/S2162253123001622MT: Delivery StrategiesnanodiamondsMicroRNAbreast cancergene deliverynanomedicine |
| spellingShingle | Marianna Abate Angela Lombardi Amalia Luce Manuela Porru Carlo Leonetti Marco Bocchetti Virginia Campani Giuseppe De Rosa Sossio Fabio Graziano Valeria Nele Francesco Cardile Federica Zito Marino Renato Franco Andrea Ronchi Marianna Scrima Rossella Sperlongano Roberto Alfano Gabriella Misso Evzen Amler Michele Caraglia Silvia Zappavigna Fluorescent nanodiamonds as innovative delivery systems for MiR-34a replacement in breast cancer Molecular Therapy: Nucleic Acids MT: Delivery Strategies nanodiamonds MicroRNA breast cancer gene delivery nanomedicine |
| title | Fluorescent nanodiamonds as innovative delivery systems for MiR-34a replacement in breast cancer |
| title_full | Fluorescent nanodiamonds as innovative delivery systems for MiR-34a replacement in breast cancer |
| title_fullStr | Fluorescent nanodiamonds as innovative delivery systems for MiR-34a replacement in breast cancer |
| title_full_unstemmed | Fluorescent nanodiamonds as innovative delivery systems for MiR-34a replacement in breast cancer |
| title_short | Fluorescent nanodiamonds as innovative delivery systems for MiR-34a replacement in breast cancer |
| title_sort | fluorescent nanodiamonds as innovative delivery systems for mir 34a replacement in breast cancer |
| topic | MT: Delivery Strategies nanodiamonds MicroRNA breast cancer gene delivery nanomedicine |
| url | http://www.sciencedirect.com/science/article/pii/S2162253123001622 |
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