Details

Autor(en) / Beteiligte

• Fracasso, Giulio
• Falvo, Elisabetta
• Colotti, Gianni
• Fazi, Francesco
• Ingegnere, Tiziano
• Amalfitano, Adriana
• Doglietto, Giovanni Battista
• Alfieri, Sergio
• Boffi, Alberto
• Morea, Veronica
• Conti, Giamaica
• Tremante, Elisa
• Giacomini, Patrizio
• Arcovito, Alessandro
• Ceci, Pierpaolo

Titel

Selective delivery of doxorubicin by novel stimuli-sensitive nano-ferritins overcomes tumor refractoriness

Ist Teil von

• Journal of controlled release, 2016-10, Vol.239, p.10-18

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• Human ferritin heavy chain (HFt) has been demonstrated to possess considerable potential for targeted delivery of drugs and diagnostic agents to cancer cells. Here, we report the development of a novel HFt-based genetic construct (HFt-MP-PAS) containing a short peptide linker (MP) between each HFt subunit and an outer shielding polypeptide sequence rich in proline (P), serine (S) and alanine (A) residues (PAS). The peptide linker contains a matrix-metalloproteinases (MMPs) cleavage site that permits the protective PAS shield to be removed by tumor-driven proteolytic cleavage within the tumor microenvironment. For the first time HFt-MP-PAS ability to deliver doxorubicin to cancer cells, subcellular localization, and therapeutic efficacy on a xenogeneic mouse model of a highly refractory to conventional chemotherapeutics type of cancer were evaluated. HFt-MP-PAS-DOXO performance was compared with the novel albumin-based drug delivery system INNO-206, currently in phase III clinical trials. The results of this work provide solid evidence indicating that the stimuli-sensitive, long-circulating HFt-MP-PAS nanocarriers described herein have the potential to be exploited in cancer therapy. [Display omitted]