SPIONs Embedded in Polyamino acid Nanogels to Synergistically Treat Tumor Microenvironment and Breast Cancer Cells

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Abstract

The extremely complex tumor microenvironment (TME) in humans is the major responsible for the therapeutic failure in cancer nanomedicine. A new concept of disease-driven nanomedicine, henceforth named "Theranomics", which attempts to target cancer cells and TME on the whole, represents an attractive alternative. Herein, a nanomedicine able to co-deliver doxorubicin and a tumor suppressive proteolytic protein such as collagenase-2 was developed. We successfully obtained superparamagnetic nanogels (SPIONs/Doco@Col) via the intermolecular azide-alkyne Huisgen cycloaddition. We demonstrated that a local ECM degradation and remodeling in solid tumors by means of collagenase-2 could enhance tumor penetration of nanomedicines and the in situ sustained release of the drug payload throughout 3-D tumor spheroids up to the core (parenchyma), thus enabling a synergistic and efficient anticancer effect toward highly invasive breast tumors. We illustrate that SPIONs/Doxo@Col is also capable of reducing the invasivity of cancer cells.
LinguaEnglish
Pagine207-219
Number of pages13
RivistaInternational Journal of Pharmaceutics
Volume555
Publication statusPublished - 2019

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title = "SPIONs Embedded in Polyamino acid Nanogels to Synergistically Treat Tumor Microenvironment and Breast Cancer Cells",
abstract = "The extremely complex tumor microenvironment (TME) in humans is the major responsible for the therapeutic failure in cancer nanomedicine. A new concept of disease-driven nanomedicine, henceforth named {"}Theranomics{"}, which attempts to target cancer cells and TME on the whole, represents an attractive alternative. Herein, a nanomedicine able to co-deliver doxorubicin and a tumor suppressive proteolytic protein such as collagenase-2 was developed. We successfully obtained superparamagnetic nanogels (SPIONs/Doco@Col) via the intermolecular azide-alkyne Huisgen cycloaddition. We demonstrated that a local ECM degradation and remodeling in solid tumors by means of collagenase-2 could enhance tumor penetration of nanomedicines and the in situ sustained release of the drug payload throughout 3-D tumor spheroids up to the core (parenchyma), thus enabling a synergistic and efficient anticancer effect toward highly invasive breast tumors. We illustrate that SPIONs/Doxo@Col is also capable of reducing the invasivity of cancer cells.",
author = "{Puleio, R.; Varvar{\`a}, P.} and Gaetano Giammona and Gennara Cavallaro and Paola Varvara' and Mariano Licciardi and Cinzia Scialabba and Nicol{\`o} Mauro",
year = "2019",
language = "English",
volume = "555",
pages = "207--219",
journal = "International Journal of Pharmaceutics",
issn = "0378-5173",
publisher = "Elsevier",

}

TY - JOUR

T1 - SPIONs Embedded in Polyamino acid Nanogels to Synergistically Treat Tumor Microenvironment and Breast Cancer Cells

AU - Puleio, R.; Varvarà, P.

AU - Giammona, Gaetano

AU - Cavallaro, Gennara

AU - Varvara', Paola

AU - Licciardi, Mariano

AU - Scialabba, Cinzia

AU - Mauro, Nicolò

PY - 2019

Y1 - 2019

N2 - The extremely complex tumor microenvironment (TME) in humans is the major responsible for the therapeutic failure in cancer nanomedicine. A new concept of disease-driven nanomedicine, henceforth named "Theranomics", which attempts to target cancer cells and TME on the whole, represents an attractive alternative. Herein, a nanomedicine able to co-deliver doxorubicin and a tumor suppressive proteolytic protein such as collagenase-2 was developed. We successfully obtained superparamagnetic nanogels (SPIONs/Doco@Col) via the intermolecular azide-alkyne Huisgen cycloaddition. We demonstrated that a local ECM degradation and remodeling in solid tumors by means of collagenase-2 could enhance tumor penetration of nanomedicines and the in situ sustained release of the drug payload throughout 3-D tumor spheroids up to the core (parenchyma), thus enabling a synergistic and efficient anticancer effect toward highly invasive breast tumors. We illustrate that SPIONs/Doxo@Col is also capable of reducing the invasivity of cancer cells.

AB - The extremely complex tumor microenvironment (TME) in humans is the major responsible for the therapeutic failure in cancer nanomedicine. A new concept of disease-driven nanomedicine, henceforth named "Theranomics", which attempts to target cancer cells and TME on the whole, represents an attractive alternative. Herein, a nanomedicine able to co-deliver doxorubicin and a tumor suppressive proteolytic protein such as collagenase-2 was developed. We successfully obtained superparamagnetic nanogels (SPIONs/Doco@Col) via the intermolecular azide-alkyne Huisgen cycloaddition. We demonstrated that a local ECM degradation and remodeling in solid tumors by means of collagenase-2 could enhance tumor penetration of nanomedicines and the in situ sustained release of the drug payload throughout 3-D tumor spheroids up to the core (parenchyma), thus enabling a synergistic and efficient anticancer effect toward highly invasive breast tumors. We illustrate that SPIONs/Doxo@Col is also capable of reducing the invasivity of cancer cells.

UR - http://hdl.handle.net/10447/319096

M3 - Article

VL - 555

SP - 207

EP - 219

JO - International Journal of Pharmaceutics

T2 - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

ER -