title: L-Ferritin targets breast cancer stem cells and delivers therapeutic and imaging agents.
abstract: A growing body of evidence suggests that cancer stem cells (CSC) have the unique biological properties necessary for tumor maintenance and spreading, and function as a reservoir for the relapse and metastatic evolution of the disease by virtue of their resistance to radio- and chemo-therapies. Thus, the efficacy of a therapeutic approach relies on its ability to effectively target and deplete CSC. In this study, we show that CSC-enriched tumorspheres from breast cancer cell lines display an increased L-Ferritin uptake capability compared to their monolayer counterparts as a consequence of the upregulation of the L-Ferritin receptor SCARA5. L-Ferritin internalization was exploited for the simultaneous delivery of Curcumin, a natural therapeutic molecule endowed with antineoplastic action, and the MRI contrast agent Gd-HPDO3A, both entrapped in the L-Ferritin cavity. This theranostic system was able to impair viability and self-renewal of tumorspheres in vitro and to induce the regression of established tumors in mice. In conclusion, here we show that Curcumin-loaded L-Ferritin has a strong therapeutic potential due to the specific targeting of CSC and the improved Curcumin bioavailability, opening up the possibility of its use in a clinical setting.
authors: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Turin, Turin, Italy.
authors: Laura
authors: L
authors: Conti
authors: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Turin, Turin, Italy.
authors: Stefania
authors: S
authors: Lanzardo
authors: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Turin, Turin, Italy.
authors: Roberto
authors: R
authors: Ruiu
authors: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Turin, Turin, Italy.
authors: Marta
authors: M
authors: Cadenazzi
authors: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Turin, Turin, Italy.
authors: Federica
authors: F
authors: Cavallo
authors: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Turin, Turin, Italy.
authors: Silvio
authors: S
authors: Aime
authors: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Turin, Turin, Italy.
authors: Simonetta
authors: S
authors: Geninatti Crich
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D001052:Apoferritins / Q000493:pharmacokinetics* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000493:pharmacokinetics; D003474:Curcumin / Q000493:pharmacokinetics* / Q000494:pharmacology; D005260:Female; D005682:Gadolinium / Q000493:pharmacokinetics; D006571:Heterocyclic Compounds / Q000493:pharmacokinetics*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D008807:Mice, Inbred BALB C; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000378:metabolism; D018874:Spheroids, Cellular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D003287:Contrast Media; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; C511405:SCARA5 protein, mouse; D051117:Scavenger Receptors, Class A; C062402:gadoteridol; D001052:Apoferritins; D005682:Gadolinium; D003474:Curcumin
keywords: cancer stem cells; ferritin; magnetic resonance imaging; mammary tumors; theranostic agents