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

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

doi:10.1016/j.jconrel.2016.08.010

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

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

Risultato della ricerca: Contributo in rivista › Articolo in rivista › peer review

42 Citazioni (Scopus)

Abstract

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.

Lingua originale	English
pagine (da-a)	10-18-18
Rivista	Journal of Controlled Release
Volume	239
DOI	https://doi.org/10.1016/j.jconrel.2016.08.010
Stato di pubblicazione	Pubblicato - 2016

Keywords

Doxorubicin (PubChem CID: 31703)
Drug-delivery
Ferritin
INNO-206 (PubChem CID: 9810709)
Nuclear localization
PASylation
Pancreatic cancer
Protein-cage nanocarrier

Accesso al documento

10.1016/j.jconrel.2016.08.010

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Alfieri, S., Arcovito, A., Amalfitano, A., Doglietto, G., Fracasso, G., Falvo, E., Colotti, G., Fazi, F., Ingegnere, T., Boffi, A., Morea, V., Conti, G., Tremante, E., Giacomini, P., & Ceci, P. (2016). Selective delivery of doxorubicin by novel stimuli-sensitive nano-ferritins overcomes tumor refractoriness. Journal of Controlled Release, 239, 10-18-18. https://doi.org/10.1016/j.jconrel.2016.08.010

Alfieri, Sergio ; Arcovito, Alessandro ; Amalfitano, Adriana ; Doglietto, Giovanni ; Fracasso, Giulio ; Falvo, Elisabetta ; Colotti, Gianni ; Fazi, Francesco ; Ingegnere, Tiziano ; Boffi, Alberto ; Morea, Veronica ; Conti, Giamaica ; Tremante, Elisa ; Giacomini, Patrizio ; Ceci, Pierpaolo. / Selective delivery of doxorubicin by novel stimuli-sensitive nano-ferritins overcomes tumor refractoriness. In: Journal of Controlled Release. 2016 ; Vol. 239. pagg. 10-18-18.

@article{021c9b87d7874862860152965f2c44b6,

title = "Selective delivery of doxorubicin by novel stimuli-sensitive nano-ferritins overcomes tumor refractoriness",

abstract = "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.",

keywords = "Doxorubicin (PubChem CID: 31703), Drug-delivery, Ferritin, INNO-206 (PubChem CID: 9810709), Nuclear localization, PASylation, Pancreatic cancer, Protein-cage nanocarrier, Doxorubicin (PubChem CID: 31703), Drug-delivery, Ferritin, INNO-206 (PubChem CID: 9810709), Nuclear localization, PASylation, Pancreatic cancer, Protein-cage nanocarrier",

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

year = "2016",

doi = "10.1016/j.jconrel.2016.08.010",

language = "English",

volume = "239",

pages = "10--18--18",

journal = "Journal of Controlled Release",

issn = "0168-3659",

publisher = "Controlled Release Society:13355 Tenth Avenue, Suite 108:Minneapolis, MN 55441:(763)512-0909, EMAIL: registration@ardel.com",

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Alfieri, S , Arcovito, A, Amalfitano, A, Doglietto, G, Fracasso, G, Falvo, E, Colotti, G, Fazi, F, Ingegnere, T, Boffi, A, Morea, V, Conti, G, Tremante, E, Giacomini, P & Ceci, P 2016, 'Selective delivery of doxorubicin by novel stimuli-sensitive nano-ferritins overcomes tumor refractoriness', Journal of Controlled Release, vol. 239, pagg. 10-18-18. https://doi.org/10.1016/j.jconrel.2016.08.010

Selective delivery of doxorubicin by novel stimuli-sensitive nano-ferritins overcomes tumor refractoriness. / Alfieri, Sergio ; Arcovito, Alessandro; Amalfitano, Adriana; Doglietto, Giovanni; Fracasso, Giulio; Falvo, Elisabetta; Colotti, Gianni; Fazi, Francesco; Ingegnere, Tiziano; Boffi, Alberto; Morea, Veronica; Conti, Giamaica; Tremante, Elisa; Giacomini, Patrizio; Ceci, Pierpaolo.

In: Journal of Controlled Release, Vol. 239, 2016, pag. 10-18-18.

Risultato della ricerca: Contributo in rivista › Articolo in rivista › peer review

TY - JOUR

T1 - Selective delivery of doxorubicin by novel stimuli-sensitive nano-ferritins overcomes tumor refractoriness

AU - Alfieri, Sergio

AU - Arcovito, Alessandro

AU - Amalfitano, Adriana

AU - Doglietto, Giovanni

AU - Fracasso, Giulio

AU - Falvo, Elisabetta

AU - Colotti, Gianni

AU - Fazi, Francesco

AU - Ingegnere, Tiziano

AU - Boffi, Alberto

AU - Morea, Veronica

AU - Conti, Giamaica

AU - Tremante, Elisa

AU - Giacomini, Patrizio

AU - Ceci, Pierpaolo

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

KW - Doxorubicin (PubChem CID: 31703)

KW - Drug-delivery

KW - Ferritin

KW - INNO-206 (PubChem CID: 9810709)

KW - Nuclear localization

KW - PASylation

KW - Pancreatic cancer

KW - Protein-cage nanocarrier

KW - Doxorubicin (PubChem CID: 31703)

KW - Drug-delivery

KW - Ferritin

KW - INNO-206 (PubChem CID: 9810709)

KW - Nuclear localization

KW - PASylation

KW - Pancreatic cancer

KW - Protein-cage nanocarrier

UR - http://hdl.handle.net/10807/84231

U2 - 10.1016/j.jconrel.2016.08.010

DO - 10.1016/j.jconrel.2016.08.010

M3 - Article

VL - 239

SP - 10-18-18

JO - Journal of Controlled Release

JF - Journal of Controlled Release

SN - 0168-3659

ER -