Engineered Human Nanoferritin Bearing the Drug Genz-644282 for Cancer Therapy

Falvo, Elisabetta; Arcovito, Alessandro; Conti, Giamaica; Cipolla, Giuseppe; Pitea, Martina; Morea, Veronica; Damiani, Verena; Sala, Gianluca; Fracasso, Giulio; Ceci, Pierpaolo

doi:10.3390/pharmaceutics12100992

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Engineered Human Nanoferritin Bearing the Drug Genz-644282 for Cancer Therapy

^1,†,

^2,3,†

⁴,

⁵,

⁶,

¹,

⁷,

⁷

^8,*,‡

and

Pierpaolo Ceci

^1,5,*,‡

CNR–National Research Council of Italy, Institute of Molecular Biology and Pathology, 00185 Rome, Italy

Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy

Fondazione Policlinico Agostino Gemelli, IRCCS, 00168 Rome, Italy

⁴

Department of Neurological and Movement Sciences, University of Verona, 37134 Verona, Italy

⁵

Thena Biotech, 04100 Latina, Italy

⁶

Department of Biochemical Sciences, University Sapienza, 00185 Rome, Italy

⁷

Center for Advanced Studies and Technology (CAST), Department of Medical Oral and Biotechnological Sciences, University of Chieti-Pescara, 66100 Chieti, Italy

⁸

Department of Medicine, University of Verona, 37134 Verona, Italy

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

^‡

Co-senior authors.

Pharmaceutics 2020, 12(10), 992; https://doi.org/10.3390/pharmaceutics12100992

Received: 1 October 2020 / Revised: 16 October 2020 / Accepted: 16 October 2020 / Published: 20 October 2020

(This article belongs to the Special Issue Self-Assembling Smart Nanoparticles for Drug Delivery)

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Abstract

Gastrointestinal tumors, including pancreatic and colorectal cancers, represent one of the greatest public health issues worldwide, leading to a million global deaths. Recent research demonstrated that the human heavy chain ferritin (HFt) can encapsulate different types of drugs in its cavity and can bind to its receptor, CD71, in several solid and hematological tumors, thus highlighting the potential use of ferritin for tumor-targeting therapies. Here, we describe the development and characterization of a novel nanomedicine based on the HFt that is named The-0504. In particular, this novel system is a nano-assembly comprising an engineered version of HFt that entraps about 80 molecules of a potent, wide-spectrum, non-camptothecin topoisomerase I inhibitor (Genz-644282). The-0504 can be produced by a standardized pre-industrial process as a pure and homogeneously formulated product with favourable lyophilization properties. The preliminary anticancer activity was evaluated in cultured cancer cells and in a mouse model of pancreatic cancer. Overall results reported here make The-0504 a candidate for further preclinical development against CD-71 expressing deadly tumors. View Full-Text

Keywords: nanomedicine; human ferritin; gastrointestinal tumors; non-camptothecin topoisomerase I inhibitors; drug-delivery; CD71

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MDPI and ACS Style

Falvo, E.; Arcovito, A.; Conti, G.; Cipolla, G.; Pitea, M.; Morea, V.; Damiani, V.; Sala, G.; Fracasso, G.; Ceci, P. Engineered Human Nanoferritin Bearing the Drug Genz-644282 for Cancer Therapy. Pharmaceutics 2020, 12, 992. https://doi.org/10.3390/pharmaceutics12100992

AMA Style

Falvo E, Arcovito A, Conti G, Cipolla G, Pitea M, Morea V, Damiani V, Sala G, Fracasso G, Ceci P. Engineered Human Nanoferritin Bearing the Drug Genz-644282 for Cancer Therapy. Pharmaceutics. 2020; 12(10):992. https://doi.org/10.3390/pharmaceutics12100992

Chicago/Turabian Style

Falvo, Elisabetta, Alessandro Arcovito, Giamaica Conti, Giuseppe Cipolla, Martina Pitea, Veronica Morea, Verena Damiani, Gianluca Sala, Giulio Fracasso, and Pierpaolo Ceci. 2020. "Engineered Human Nanoferritin Bearing the Drug Genz-644282 for Cancer Therapy" Pharmaceutics 12, no. 10: 992. https://doi.org/10.3390/pharmaceutics12100992

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