Design and Synthesis of Piperazine-Based Compounds Conjugated to Humanized Ferritin as Delivery System of siRNA in Cancer Cells

N. Pediconi, F. Ghirga, Plato C. Del, G. Peruzzi, C. M. Athanassopoulos, M. Mori, M. E. Crestoni, D. Corinti, F. Ugozzoli, C. Massera, Alessandro Arcovito, B. Botta*, A. Boffi, D. Quaglio*, P. Baiocco

*Autore corrispondente per questo lavoro

Risultato della ricerca: Contributo in rivistaArticolopeer review

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.
Lingua originaleInglese
pagine (da-a)1-12
Numero di pagine12
RivistaBioconjugate Chemistry
Volume2021
Numero di pubblicazioneN/A
DOI
Stato di pubblicazionePubblicato - 2021

All Science Journal Classification (ASJC) codes

  • Biotecnologia
  • Bioingegneria
  • Ingegneria Biomedica
  • Farmacologia
  • Scienze Farmaceutiche
  • Chimica Organica

Keywords

  • humanized ferritin
  • piperazine based compounds
  • siRNA

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