L-Ferritin targets breast cancer stem cells and delivers therapeutic and imaging agents

• Published in: Oncotarget 2016-10, Vol.7 (41), p.66713-66727
• Main Authors: Conti, Laura, Lanzardo, Stefania, Ruiu, Roberto, Cadenazzi, Marta, Cavallo, Federica, Aime, Silvio, Geninatti Crich, Simonetta
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - pharmacology; Apoferritins - pharmacokinetics; Apoferritins - pharmacology; Breast Neoplasms - diagnostic imaging; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell Line, Tumor; Contrast Media - pharmacokinetics; Curcumin - pharmacokinetics; Curcumin - pharmacology; Female; Gadolinium - pharmacokinetics; Heterocyclic Compounds - pharmacokinetics; Humans; Magnetic Resonance Imaging; Mammary Neoplasms, Experimental - drug therapy; Mammary Neoplasms, Experimental - genetics; Mammary Neoplasms, Experimental - metabolism; Mice, Inbred BALB C; Neoplastic Stem Cells - drug effects; Neoplastic Stem Cells - metabolism; Organometallic Compounds - pharmacokinetics; Research Paper; Scavenger Receptors, Class A - genetics; Scavenger Receptors, Class A - metabolism; Spheroids, Cellular - drug effects; Spheroids, Cellular - metabolism; Spheroids, Cellular - pathology
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.10920

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.