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

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

doi:10.1016/j.jconrel.2016.08.010

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

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

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

43 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

OSS delle Nazioni Unite

Questo processo contribuisce al raggiungimento dei seguenti obiettivi di sviluppo sostenibile

Accesso al documento

10.1016/j.jconrel.2016.08.010

Altri file e collegamenti

Link a IRIS PubliCatt

Cita questo

Fracasso, G., Falvo, E., Colotti, G., Fazi, F., Ingegnere, T., Amalfitano, A., Doglietto, G., Alfieri, S., Boffi, A., Morea, V., Conti, G., Tremante, E., Giacomini, P., Arcovito, A., & 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

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

}

Fracasso, G, Falvo, E, Colotti, G, Fazi, F, Ingegnere, T, Amalfitano, A, Doglietto, G, Alfieri, S, Boffi, A, Morea, V, Conti, G, Tremante, E, Giacomini, P, Arcovito, A & 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

TY - JOUR

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

AU - Fracasso, Giulio

AU - Falvo, Elisabetta

AU - Colotti, Gianni

AU - Fazi, Francesco

AU - Ingegnere, Tiziano

AU - Amalfitano, Adriana

AU - Doglietto, Giovanni

AU - Alfieri, Sergio

AU - Boffi, Alberto

AU - Morea, Veronica

AU - Conti, Giamaica

AU - Tremante, Elisa

AU - Giacomini, Patrizio

AU - Arcovito, Alessandro

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

SN - 0168-3659

VL - 239

SP - 10-18-18

JO - Journal of Controlled Release

JF - Journal of Controlled Release

ER -

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

Abstract

Keywords

OSS delle Nazioni Unite

Accesso al documento

Altri file e collegamenti

Fingerprint

Cita questo