Targeting ferritin receptors for the selective delivery of imaging and therapeutic agents to breast cancer cells.

In this work the selective uptake of native horse spleen ferritin and apoferritin loaded with MRI contrast agents has been assessed in human breast cancer cells (MCF-7 and MDA-MB-231). The higher expression of L-ferritin receptors (SCARA5) led to an enhanced uptake in MCF-7 as shown in T2 and T1 weighted MR images, respectively. The high efficiency of ferritin internalization in MCF-7 has been exploited for the simultaneous delivery of curcumin, a natural therapeutic molecule endowed with antineoplastic and anti-inflammatory action, and the MRI contrast agent Gd-HPDO3A. This theranostic system is able to treat selectively breast cancer cells over-expressing ferritin receptors. By entrapping in apoferritin both Gd-HPDO3A and curcumin, it was possible to deliver a therapeutic dose of 167 μg ml(-1) (as calculated by MRI) of this natural drug to MCF-7 cells, thus obtaining a significant reduction of cell proliferation.

[1]  J. Connor,et al.  Ferritin stimulates breast cancer cells through an iron-independent mechanism and is localized within tumor-associated macrophages , 2013, Breast Cancer Research and Treatment.

[2]  G. G. Stokes "J." , 1890, The New Yale Book of Quotations.

[3]  S. Aime,et al.  Reduction/dissolution of a beta-MnOOH nanophase in the ferritin cavity to yield a highly sensitive, biologically compatible magnetic resonance imaging agent. , 2010, Angewandte Chemie.

[4]  W. Seaman,et al.  Binding and uptake of H-ferritin are mediated by human transferrin receptor-1 , 2010, Proceedings of the National Academy of Sciences.

[5]  Zhiwei Chen,et al.  The Effect of Curcumin on Breast Cancer Cells , 2013, Journal of breast cancer.

[6]  Murali M. Yallapu,et al.  Curcumin nanoformulations: a future nanomedicine for cancer. , 2012, Drug discovery today.

[7]  Jun Wang,et al.  Protein-based nanomedicine platforms for drug delivery. , 2009, Small.

[8]  G. Rimbach,et al.  Curcumin--from molecule to biological function. , 2012, Angewandte Chemie.

[9]  K. Lukong,et al.  New targeted therapies for breast cancer: A focus on tumor microenvironmental signals and chemoresistant breast cancers. , 2014, World journal of clinical cases.

[10]  S. Aime,et al.  Curcumin/Gd loaded apoferritin: a novel "theranostic" agent to prevent hepatocellular damage in toxic induced acute hepatitis. , 2013, Molecular pharmaceutics.

[11]  Murali M. Yallapu,et al.  Curcumin nanomedicine: a road to cancer therapeutics. , 2013, Current pharmaceutical design.

[12]  R. Muller,et al.  Relaxation induced by ferritin: a better understanding for an improved MRI iron quantification , 2004, NMR in biomedicine.

[13]  Shirley Dex,et al.  JR 旅客販売総合システム(マルス)における運用及び管理について , 1991 .

[14]  H. Gómez,et al.  Breast cancer in young women in Latin America: an unmet, growing burden. , 2013, The oncologist.

[15]  Wim E Hennink,et al.  Curcumin nanoformulations: a review of pharmaceutical properties and preclinical studies and clinical data related to cancer treatment. , 2014, Biomaterials.

[16]  O. Kovalchuk,et al.  Role of ferritin alterations in human breast cancer cells , 2011, Breast Cancer Research and Treatment.

[17]  P. Cochat,et al.  Et al , 2008, Archives de pediatrie : organe officiel de la Societe francaise de pediatrie.

[18]  L. Tei,et al.  Magnetic resonance visualization of tumor angiogenesis by targeting neural cell adhesion molecules with the highly sensitive gadolinium-loaded apoferritin probe. , 2006, Cancer research.

[19]  Zipeng Zhen,et al.  Ferritins as nanoplatforms for imaging and drug delivery , 2014, Expert Opinion on Drug Delivery.

[20]  M. Preusser,et al.  The landscape of medical oncology in Europe by 2020. , 2014, Annals of oncology : official journal of the European Society for Medical Oncology.

[21]  M. Willingham,et al.  Iron Uptake Mediated by Binding of H-Ferritin to the TIM-2 Receptor in Mouse Cells , 2011, PloS one.

[22]  Dongling Yang,et al.  H-ferritin–nanocaged doxorubicin nanoparticles specifically target and kill tumors with a single-dose injection , 2014, Proceedings of the National Academy of Sciences.

[23]  Val Gebski,et al.  Capecitabine versus classical cyclophosphamide, methotrexate, and fluorouracil as first-line chemotherapy for advanced breast cancer. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[24]  Enzo Terreno,et al.  Effect of the intracellular localization of a Gd‐based imaging probe on the relaxation enhancement of water protons , 2006, Magnetic resonance in medicine.

[25]  J. Connor,et al.  The significance of ferritin in cancer: anti-oxidation, inflammation and tumorigenesis. , 2013, Biochimica et biophysica acta.

[26]  Simone Sanna-Cherchi,et al.  Scara5 is a ferritin receptor mediating non-transferrin iron delivery. , 2009, Developmental cell.

[27]  Michel Luhmer,et al.  Effect of magnetic field and iron content on NMR proton relaxation of liver, spleen and brain tissues. , 2015, Contrast media & molecular imaging.

[28]  Jin Xie,et al.  RGD-modified apoferritin nanoparticles for efficient drug delivery to tumors. , 2013, ACS nano.

[29]  Klaas Nicolay,et al.  Cellular compartmentalization of internalized paramagnetic liposomes strongly influences both T1 and T2 relaxivity , 2009, Magnetic resonance in medicine.

[30]  A. Iolascon,et al.  Mn-loaded apoferritin: a highly sensitive MRI imaging probe for the detection and characterization of hepatocarcinoma lesions in a transgenic mouse model. , 2012, Contrast media & molecular imaging.

[31]  R. Muller,et al.  Relaxivities of human liver and spleen ferritin. , 2005, Magnetic resonance imaging.

[32]  J. Connor,et al.  Ferritin: a novel mechanism for delivery of iron to the brain and other organs. , 2007, American journal of physiology. Cell physiology.

[33]  Miss A.O. Penney (b) , 1974, The New Yale Book of Quotations.

[34]  Lin Mei,et al.  Nanotheranostics ˗ Application and Further Development of Nanomedicine Strategies for Advanced Theranostics , 2014, Theranostics.

[35]  Guodong Liu,et al.  Apoferritin-templated synthesis of metal phosphate nanoparticle labels for electrochemical immunoassay. , 2006, Small.

[36]  J. Kaplan,et al.  A Tf-independent iron transport system required for organogenesis. , 2009, Developmental cell.

[37]  Yuehe Lin,et al.  Apoferritin-templated yttrium phosphate nanoparticle conjugates for radioimmunotherapy of cancers. , 2008, Journal of nanoscience and nanotechnology.

[38]  S. Çalış,et al.  A novel protein-based anticancer drug encapsulating nanosphere: apoferritin-doxorubicin complex. , 2012, Journal of biomedical nanotechnology.

[39]  Ze-Guang Han,et al.  Genetic and epigenetic silencing of SCARA5 may contribute to human hepatocellular carcinoma by activating FAK signaling. , 2010, The Journal of clinical investigation.

[40]  F. Torti,et al.  Serum ferritin: Past, present and future. , 2010, Biochimica et biophysica acta.

[41]  B. Todorich,et al.  Tim‐2 is the receptor for H‐ferritin on oligodendrocytes , 2008, Journal of neurochemistry.

[42]  Fabian Kiessling,et al.  Recent progress in nanomedicine: therapeutic, diagnostic and theranostic applications. , 2013, Current opinion in biotechnology.

[43]  J. Zhao,et al.  Epidermal growth factor-ferritin H-chain protein nanoparticles for tumor active targeting. , 2012, Small.

[44]  Silvio Aime,et al.  Compartmentalization of a gadolinium complex in the apoferritin cavity: a route to obtain high relaxivity contrast agents for magnetic resonance imaging. , 2002, Angewandte Chemie.