Chronic lymphocytic leukemia (CLL) is a widespread type of leukemia that predominantly targets B lymphocytes, undermining the balance between cell proliferation and apoptosis. In healthy B cells, miR-15/16, a tandem of microRNAs, functions as a tumor suppressor, curbing the expression of the antiapoptotic B cell lymphoma 2 protein (Bcl-2). Conversely, in CLL patients, a recurring deletion on chromosome 13q14, home to the miR15-a and miR16-1 genes, results in Bcl-2 overexpression, thereby fostering the onset of the pathology. In the present research, a novel approach utilizing humanized ferritin-based nanoparticles was employed to successfully deliver miR15-a and miR- 16-1 into MEG01 cells, a model characterized by the classic CLL deletion and overexpression of the human ferritin receptor (TfR1). The loaded miR15-a and miR16-1, housed within modified HumAfFt, were efficiently internalized via the MEG01 cells and properly directed into the cytoplasm. Impressively, the concurrent application of miR15-a and miR16-1 demonstrated a robust capacity to induce apoptosis through the reduction in Bcl-2 expression levels. This technology, employing RNA-loaded ferritin nanoparticles, hints at promising directions in the battle against CLL, bridging the substantial gap left by traditional transfection agents and indicating a pathway that may offer hope for more effective treatments.

Combined delivery of miR-15/16 through humanized ferritin nanocages for the treatment of chronic lymphocytic leukemia / Liberati, FRANCESCA ROMANA; DI RUSSO, Sara; Barolo, Lorenzo; Peruzzi, Giovanna; Farina, MARIA VITTORIA; Spizzichino, Sharon; DI FONZO, Federica; Quaglio, Deborah; Pisano, Luca; Botta, Bruno; Giorgi, Alessandra; Boffi, Alberto; Cutruzzola, Francesca; Paone, Alessio; Baiocco, Paola. - In: PHARMACEUTICS. - ISSN 1999-4923. - 16:402(2024). [10.3390/pharmaceutics16030402]

Combined delivery of miR-15/16 through humanized ferritin nanocages for the treatment of chronic lymphocytic leukemia

Francesca Romana Liberati
Methodology
;
Sara Di Russo
Methodology
;
Lorenzo Barolo
Methodology
;
Maria Vittoria Farina
Methodology
;
Sharon Spizzichino
Methodology
;
Federica Di Fonzo
Methodology
;
Deborah Quaglio
Validation
;
Luca Pisano
Methodology
;
Bruno Botta
Funding Acquisition
;
Alessandra Giorgi
Methodology
;
Alberto Boffi
Funding Acquisition
;
Francesca Cutruzzola
Funding Acquisition
;
Alessio Paone
Project Administration
;
Paola Baiocco
Project Administration
2024

Abstract

Chronic lymphocytic leukemia (CLL) is a widespread type of leukemia that predominantly targets B lymphocytes, undermining the balance between cell proliferation and apoptosis. In healthy B cells, miR-15/16, a tandem of microRNAs, functions as a tumor suppressor, curbing the expression of the antiapoptotic B cell lymphoma 2 protein (Bcl-2). Conversely, in CLL patients, a recurring deletion on chromosome 13q14, home to the miR15-a and miR16-1 genes, results in Bcl-2 overexpression, thereby fostering the onset of the pathology. In the present research, a novel approach utilizing humanized ferritin-based nanoparticles was employed to successfully deliver miR15-a and miR- 16-1 into MEG01 cells, a model characterized by the classic CLL deletion and overexpression of the human ferritin receptor (TfR1). The loaded miR15-a and miR16-1, housed within modified HumAfFt, were efficiently internalized via the MEG01 cells and properly directed into the cytoplasm. Impressively, the concurrent application of miR15-a and miR16-1 demonstrated a robust capacity to induce apoptosis through the reduction in Bcl-2 expression levels. This technology, employing RNA-loaded ferritin nanoparticles, hints at promising directions in the battle against CLL, bridging the substantial gap left by traditional transfection agents and indicating a pathway that may offer hope for more effective treatments.
2024
ferritin nanocages; Bcl-2; miR-15a; miR-16-1 delivery; leukemia; self-assembly
01 Pubblicazione su rivista::01a Articolo in rivista
Combined delivery of miR-15/16 through humanized ferritin nanocages for the treatment of chronic lymphocytic leukemia / Liberati, FRANCESCA ROMANA; DI RUSSO, Sara; Barolo, Lorenzo; Peruzzi, Giovanna; Farina, MARIA VITTORIA; Spizzichino, Sharon; DI FONZO, Federica; Quaglio, Deborah; Pisano, Luca; Botta, Bruno; Giorgi, Alessandra; Boffi, Alberto; Cutruzzola, Francesca; Paone, Alessio; Baiocco, Paola. - In: PHARMACEUTICS. - ISSN 1999-4923. - 16:402(2024). [10.3390/pharmaceutics16030402]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1707844
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