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: Laura Conti, Stefania Lanzardo, Roberto Ruiu, Marta Cadenazzi, Federica Cavallo, Silvio Aime, Simonetta Geninatti Crich
• Journal: Oncotarget (Oncotarget) Vol. 7 Issue 41 Pg. 66713-66727 (Oct 11 2016) ISSN: 1949-2553 [Electronic] United States
• PMID: 27579532 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Contrast Media
• Heterocyclic Compounds
• Organometallic Compounds
• SCARA5 protein, mouse
• Scavenger Receptors, Class A
• gadoteridol
• Apoferritins
• Gadolinium
• Curcumin

Topics

• Animals
• Antineoplastic Agents (pharmacokinetics, pharmacology)
• Apoferritins (pharmacokinetics, pharmacology)
• Breast Neoplasms (diagnostic imaging, metabolism, pathology)
• Cell Line, Tumor
• Contrast Media (pharmacokinetics)
• Curcumin (pharmacokinetics, pharmacology)
• Female
• Gadolinium (pharmacokinetics)
• Heterocyclic Compounds (pharmacokinetics)
• Humans
• Magnetic Resonance Imaging
• Mammary Neoplasms, Experimental (drug therapy, genetics, metabolism)
• Mice, Inbred BALB C
• Neoplastic Stem Cells (drug effects, metabolism)
• Organometallic Compounds (pharmacokinetics)
• Scavenger Receptors, Class A (genetics, metabolism)
• Spheroids, Cellular (drug effects, metabolism, pathology)