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.

NK cells control breast cancer and related cancer stem cell hematological spread

“…Interestingly, we have previously reported that tumorspheres maintain a prevalent CSC phenotype after in vivo injection. 27 As reported in Fig. 4, a lower frequency of H2-K d and a higher frequency and expression of activating ligands, RAE, H60, PVR and Nectin-2, were observed in both the tumorsphere-generated tumors and metastases than in their TUBO-generated analogs.…”

Thermostability of protein nanocages: the effect of natural extra peptide on the exterior surface

“…We wonder whether such extra peptide can also be utilized to improve the thermostability of animal ferritin such as HuHF because it has emerged as a popular biotemplate or vehicle in the eld of nanotechnology and nanomedicine. [14][15][16][17][18][19] To this end, we prepared a HuHF mutant termed HuHF-VEP where EP was connected to the N-terminal of HuHF subunit by genetic modication. Aer E. coli cells expressing this mutant were lysed, we puried it to homogeneity as suggested by SDS and native PAGE ( Fig.…”

“…[10][11][12] Beneting from the low immunogenicity and the high selectivity for cancer cells which overexpress transferrin receptor 1 (TfR1) for human H-chain ferritin (HuHF), 13 ferritin especially human H-chain ferritin, has attracted attention in materials and medicinal chemistry with use of ferritin nanocages as a vehicle for tumor-imaging agents, anticancer drugs, and bioactive nutrients. [14][15][16][17][18][19] The structure of plant ferritin is different from that of animal ferritin in that plant ferritin only consists of H-type subunits which usually contain an extra peptide (EP) (about 30 amino acid residues) at its N-terminal extremity, while animal ferritin is devoid of such EP domain. 20 This EP domain exhibited the serine-like protease activity and contributed to the storage stability of ferritin.…”

Ferritin: A Platform for MRI Contrast Agents Delivery

“…The encapsulation of Curcumin inside the apoferritin cavity significantly increases its stability and bioavailability while maintaining its therapeutic anti-inflammatory properties [73]. More recently, the theranostic potential of Apo-CUR-Gd was assessed on cancer stem cells (CSCs) [74]. Most evidence suggests that CSCs 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 [75].…”