Combined Delivery of miR-15/16 through Humanized Ferritin Nanocages for the Treatment of Chronic Lymphocytic Leukemia

Francesca Romana Liberati; Sara Di Russo; Lorenzo Barolo; Giovanna Peruzzi; Maria Vittoria Farina; Sharon Spizzichino; Federica Di Fonzo; Deborah Quaglio; Luca Pisano; Bruno Botta; Alessandra Giorgi; Alberto Boffi; Francesca Cutruzzolà; Alessio Paone; Paola Baiocco

doi:10.3390/pharmaceutics16030402

Pharmaceutics (Mar 2024)

Combined Delivery of miR-15/16 through Humanized Ferritin Nanocages for the Treatment of Chronic Lymphocytic Leukemia

Francesca Romana Liberati,
Sara Di Russo,
Lorenzo Barolo,
Giovanna Peruzzi,
Maria Vittoria Farina,
Sharon Spizzichino,
Federica Di Fonzo,
Deborah Quaglio,
Luca Pisano,
Bruno Botta,
Alessandra Giorgi,
Alberto Boffi,
Francesca Cutruzzolà,
Alessio Paone,
Paola Baiocco

Affiliations

Francesca Romana Liberati: Department of Biochemical Sciences “Alessandro Rossi Fanelli”, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy
Sara Di Russo: Department of Biochemical Sciences “Alessandro Rossi Fanelli”, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy
Lorenzo Barolo: Department of Biochemical Sciences “Alessandro Rossi Fanelli”, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy
Giovanna Peruzzi: Center for Life Nano- & Neuro-Science@Sapienza, Istituto Italiano di Tecnologia, V.le Regina Elena 291, 00161 Rome, Italy
Maria Vittoria Farina: Department of Biochemical Sciences “Alessandro Rossi Fanelli”, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy
Sharon Spizzichino: Department of Biochemical Sciences “Alessandro Rossi Fanelli”, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy
Federica Di Fonzo: Department of Biochemical Sciences “Alessandro Rossi Fanelli”, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy
Deborah Quaglio: Department of Chemistry and Technology of Drugs, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy
Luca Pisano: Department of Chemistry and Technology of Drugs, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy
Bruno Botta: University of Rome UnitelmaSapienza, Piazza Sassari 4, 00161 Rome, Italy
Alessandra Giorgi: Department of Biochemical Sciences “Alessandro Rossi Fanelli”, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy
Alberto Boffi: Department of Biochemical Sciences “Alessandro Rossi Fanelli”, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy
Francesca Cutruzzolà: Department of Biochemical Sciences “Alessandro Rossi Fanelli”, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy
Alessio Paone: Department of Biochemical Sciences “Alessandro Rossi Fanelli”, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy
Paola Baiocco: Department of Biochemical Sciences “Alessandro Rossi Fanelli”, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy

DOI: https://doi.org/10.3390/pharmaceutics16030402
Journal volume & issue: Vol. 16, no. 3
p. 402

Abstract

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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.

Published in Pharmaceutics

ISSN: 1999-4923 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Pharmacy and materia medica
Website: http://www.mdpi.com/journal/pharmaceutics/

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