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

MT: Delivery Strategies MiR-34a MicroRNA breast cancer gene delivery gene therapy miRNA replacement therapy nanodiamonds nanomedicine nanotechnology

Journal

Molecular therapy. Nucleic acids
ISSN: 2162-2531
Titre abrégé: Mol Ther Nucleic Acids
Pays: United States
ID NLM: 101581621

Informations de publication

Date de publication:
12 Sep 2023
Historique:
received: 06 04 2023
accepted: 14 06 2023
medline: 14 7 2023
pubmed: 14 7 2023
entrez: 14 7 2023
Statut: epublish

Résumé

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.

Identifiants

pubmed: 37449042
doi: 10.1016/j.omtn.2023.06.012
pii: S2162-2531(23)00162-2
pmc: PMC10336355
doi:

Types de publication

Journal Article

Langues

eng

Pagination

127-141

Informations de copyright

© 2023 The Author(s).

Déclaration de conflit d'intérêts

The all authors declare that they have no conflicts of interests.

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Auteurs

Marianna Abate (M)

Department 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 Republic.

Angela Lombardi (A)

Department of Precision Medicine, University of Campania "Luigi Vanvitelli," Via L. De Crecchio 7, 80138 Naples, Italy.

Amalia Luce (A)

Department of Precision Medicine, University of Campania "Luigi Vanvitelli," Via L. De Crecchio 7, 80138 Naples, Italy.

Manuela Porru (M)

Translational Oncology Research Unit, IRCCS Regina Elena National Cancer Institute, E Chianesi 53, 00144 Rome, Italy.

Carlo Leonetti (C)

Translational Oncology Research Unit, IRCCS Regina Elena National Cancer Institute, E Chianesi 53, 00144 Rome, Italy.

Marco Bocchetti (M)

Department 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.

Virginia Campani (V)

Department of Pharmacy, University of Naples Federico II, D. Montesano 49, 80131 Naples, Italy.

Giuseppe De Rosa (G)

Department of Pharmacy, University of Naples Federico II, D. Montesano 49, 80131 Naples, Italy.

Sossio Fabio Graziano (SF)

Department of Pharmacy, University of Naples Federico II, D. Montesano 49, 80131 Naples, Italy.

Valeria Nele (V)

Department of Pharmacy, University of Naples Federico II, D. Montesano 49, 80131 Naples, Italy.

Francesco Cardile (F)

Laboratory of Precision and Molecular Oncology, Biogem Scarl, Institute of Genetic Research, Contrada Camporeale, 83031 Ariano Irpino, Italy.

Federica Zito Marino (FZ)

Department of Mental and Physical Health and Preventive Medicine, Pathology Unit, University of Campania "Luigi Vanvitelli," 80138 Naples, Italy.

Renato Franco (R)

Department of Mental and Physical Health and Preventive Medicine, Pathology Unit, University of Campania "Luigi Vanvitelli," 80138 Naples, Italy.

Andrea Ronchi (A)

Department of Mental and Physical Health and Preventive Medicine, Pathology Unit, University of Campania "Luigi Vanvitelli," 80138 Naples, Italy.

Marianna Scrima (M)

Laboratory of Precision and Molecular Oncology, Biogem Scarl, Institute of Genetic Research, Contrada Camporeale, 83031 Ariano Irpino, Italy.

Rossella Sperlongano (R)

Department of Precision Medicine, University of Campania "Luigi Vanvitelli," Via L. De Crecchio 7, 80138 Naples, Italy.

Roberto Alfano (R)

Department of Advanced Medical and Surgical Sciences "DAMSS," University of Campania "Luigi Vanvitelli," Via S. M. di Costantinopoli 104, 80138 Naples, Italy.

Gabriella Misso (G)

Department of Precision Medicine, University of Campania "Luigi Vanvitelli," Via L. De Crecchio 7, 80138 Naples, Italy.

Evzen Amler (E)

Department 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 Republic.

Michele Caraglia (M)

Department 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.

Silvia Zappavigna (S)

Department of Precision Medicine, University of Campania "Luigi Vanvitelli," Via L. De Crecchio 7, 80138 Naples, Italy.

Classifications MeSH