Gene expression regulation by small interfering RNA (siRNA) holds promise in treating a wide range of diseases through selective gene silencing. However, successful clinical application of nucleic acid-based therapy requires novel delivery options. Herein, to achieve efficient delivery of negatively charged siRNA duplexes, the internal cavity of "humanized" chimeric Archaeal ferritin (HumAfFt) was specifically decorated with novel cationic piperazine-based compounds (PAs). By coupling these rigid-rod-like amines with thiol-reactive reagents, chemoselective conjugation was efficiently afforded on topologically selected cysteine residues properly located inside HumAfFt. The capability of PAs-HumAfFt to host and deliver siRNA molecules through human transferrin receptor (TfR1), overexpressed in many cancer cells, was explored. These systems allowed siRNA delivery into HeLa, HepG2, and MCF-7 cancer cells with improved silencing effect on glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene expression with respect to traditional transfection methodologies and provided a promising TfR1-targeting system for multifunctional siRNA delivery to therapeutic applications.

Design and synthesis of piperazine-based compounds conjugated to humanized ferritin as delivery system of siRNA in cancer cells / Pediconi, Natalia; Ghirga, Francesca; Del Plato, Cristina; Peruzzi, Giovanna; Athanassopoulos, Constantinos M; Mori, Mattia; Crestoni, Maria Elisa; Corinti, Davide; Ugozzoli, Franco; Massera, Chiara; Arcovito, Alessandro; Botta, Bruno; Boffi, Alberto; Quaglio, Deborah; Baiocco, Paola. - In: BIOCONJUGATE CHEMISTRY. - ISSN 1043-1802. - (2021). [10.1021/acs.bioconjchem.1c00137]

Design and synthesis of piperazine-based compounds conjugated to humanized ferritin as delivery system of siRNA in cancer cells

Pediconi, Natalia
Co-primo
;
Ghirga, Francesca
Co-primo
;
Del Plato, Cristina;Peruzzi, Giovanna;Crestoni, Maria Elisa;Corinti, Davide;Botta, Bruno
;
Boffi, Alberto;Quaglio, Deborah
Penultimo
;
Baiocco, Paola
Ultimo
2021

Abstract

Gene expression regulation by small interfering RNA (siRNA) holds promise in treating a wide range of diseases through selective gene silencing. However, successful clinical application of nucleic acid-based therapy requires novel delivery options. Herein, to achieve efficient delivery of negatively charged siRNA duplexes, the internal cavity of "humanized" chimeric Archaeal ferritin (HumAfFt) was specifically decorated with novel cationic piperazine-based compounds (PAs). By coupling these rigid-rod-like amines with thiol-reactive reagents, chemoselective conjugation was efficiently afforded on topologically selected cysteine residues properly located inside HumAfFt. The capability of PAs-HumAfFt to host and deliver siRNA molecules through human transferrin receptor (TfR1), overexpressed in many cancer cells, was explored. These systems allowed siRNA delivery into HeLa, HepG2, and MCF-7 cancer cells with improved silencing effect on glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene expression with respect to traditional transfection methodologies and provided a promising TfR1-targeting system for multifunctional siRNA delivery to therapeutic applications.
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Note: https://pubs.acs.org/doi/10.1021/acs.bioconjchem.1c00137
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11573/1552342
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