MARTINA PITEA

Dottoressa di ricerca

ciclo: XXXIV


supervisore: Pierpaolo Ceci
relatore: Alberto Boffi

Titolo della tesi: Engineered Human Nanoferritin For Cancer Therapy: Development and Biophysical characterization

Human ferritin H-chain (HFt) nanoparticles represent one of the most appropriate vectors for cellular delivery of molecules thanks to their specific cell internalization by human Transferrin Receptor 1 (CD71), a transmembrane receptor overexpressed in most cancer cell types. In this PhD thesis I report the determination of the structure of HFt and CD71 in the form of complex, by using cryo electron microscopy (cryo-EM) technique. The two proteins have been shown to interact very tightly with nanomolar affinity, as assessed by Surface Plasmon Resonance (SPR) experiments. Our cryo-EM data unveil the residues involved in this contact and provide a sound structural basis to elaborate on the possibility of developing alternative ferritin-like anti-viral or anti-parasite therapeutic ligand, be it an antibody or a peptidomimetic capable of blocking the “common contacts” epitope on CD71 residue, and to further engineering ferritins as theranostic agents. In this thesis I also report the development and characterization, in vitro and in vivo, of two HFt-based nanovectors containing Mitoxantrone (MIT) or Genz-644282 as cancer drug payload, named HFt-MP-PASE-MIT or The-0504, respectively. The results reported here are very promising and pave the way for an effective cancer-targeted chemotherapy using our HFt-based nanovector platforms.

Produzione scientifica

11573/1646264 - 2022 - Lactoferrin inhibition of the complex formation between ACE2 receptor and SARS CoV-2 recognition binding domain
Piacentini, R.; Centi, L.; Miotto, M.; Milanetti, E.; Di Rienzo, L.; Pitea, M.; Piazza, P.; Ruocco, G.; Boffi, A.; Parisi, G. - 01a Articolo in rivista
rivista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (Basel (Matthaeustrasse 11) : Molecular Diversity Preservation International MDPI) pp. 5436- - issn: 1661-6596 - wos: WOS:000801799200001 (10) - scopus: 2-s2.0-85129810681 (10)

11573/1596700 - 2021 - Mitoxantrone-loaded nanoferritin slows tumor growth and improves the overall survival rate in a subcutaneous pancreatic cancer mouse model
Conti, G.; Pitea, M.; Ossanna, R.; Opri, R.; Tisci, G.; Falvo, E.; Innamorati, G.; Ghanem, E.; Sbarbati, A.; Ceci, P.; Fracasso, G. - 01a Articolo in rivista
rivista: BIOMEDICINES (Basel : MDPI) pp. 1622- - issn: 2227-9059 - wos: WOS:000725043400001 (2) - scopus: 2-s2.0-85119580812 (2)

11573/1490856 - 2020 - Engineered human nanoferritin bearing the drug genz-644282 for cancer therapy
Falvo, E.; Arcovito, A.; Conti, G.; Cipolla, G.; Pitea, M.; Morea, V.; Damiani, V.; Sala, G.; Fracasso, G.; Ceci, P. - 01a Articolo in rivista
rivista: PHARMACEUTICS (Basel: MDPI, 2009-) pp. 1-11 - issn: 1999-4923 - wos: WOS:000587444300001 (11) - scopus: 2-s2.0-85093671339 (12)

11573/1254997 - 2019 - Cryo-EM structure of the human ferritin–transferrin receptor 1 complex
Montemiglio, Linda Celeste; Testi, Claudia; Ceci, Pierpaolo; Falvo, Elisabetta; Pitea, Martina; Savino, Carmelinda; Arcovito, Alessandro; Peruzzi, Giovanna; Baiocco, Paola; Mancia, Filippo; Boffi, Alberto; Des Georges, Amédée; Vallone, Beatrice - 01a Articolo in rivista
rivista: NATURE COMMUNICATIONS (London: Nature Publishing Group) pp. 1121- - issn: 2041-1723 - wos: WOS:000460631100006 (95) - scopus: 2-s2.0-85062598392 (101)

11573/1255053 - 2017 - Therapeutic efficacy of the novel stimuli-sensitive nano-ferritins containing doxorubicin in a head and neck cancer model
Damiani, Verena; Falvo, Elisabetta; Fracasso, Giulio; Federici, Luca; Pitea, Martina; De Laurenzi, Vincenzo; Sala, Gianluca; Ceci, Pierpaolo - 01a Articolo in rivista
rivista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (Basel (Matthaeustrasse 11) : Molecular Diversity Preservation International MDPI) pp. 1555- - issn: 1661-6596 - wos: WOS:000408746800222 (25) - scopus: 2-s2.0-85025106016 (28)

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