Engineered Human Nanoferritin Bearing the Drug Genz-644282 for Cancer Therapy
Elisabetta Falvo,
Alessandro Arcovito,
Giamaica Conti,
Giuseppe Cipolla,
Martina Pitea,
Veronica Morea,
Verena Damiani,
Gianluca Sala,
Giulio Fracasso,
Pierpaolo Ceci
Affiliations
Elisabetta Falvo
CNR–National Research Council of Italy, Institute of Molecular Biology and Pathology, 00185 Rome, Italy
Alessandro Arcovito
Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy
Giamaica Conti
Department of Neurological and Movement Sciences, University of Verona, 37134 Verona, Italy
Giuseppe Cipolla
Thena Biotech, 04100 Latina, Italy
Martina Pitea
Department of Biochemical Sciences, University Sapienza, 00185 Rome, Italy
Veronica Morea
CNR–National Research Council of Italy, Institute of Molecular Biology and Pathology, 00185 Rome, Italy
Verena Damiani
Center for Advanced Studies and Technology (CAST), Department of Medical Oral and Biotechnological Sciences, University of Chieti-Pescara, 66100 Chieti, Italy
Gianluca Sala
Center for Advanced Studies and Technology (CAST), Department of Medical Oral and Biotechnological Sciences, University of Chieti-Pescara, 66100 Chieti, Italy
Giulio Fracasso
Department of Medicine, University of Verona, 37134 Verona, Italy
Pierpaolo Ceci
CNR–National Research Council of Italy, Institute of Molecular Biology and Pathology, 00185 Rome, Italy
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.
