Ferrocifen Loaded Lipid Nanocapsules: Comparison
View Latest Version
Please note this is a comparison between Version 2 by Conner Chen and Version 1 by Catherine Passirani.

Resistance of cancer cells to current chemotherapeutic drugs has obliged the scientific community to seek innovative compounds. Ferrocifens, lipophilic organometallic compounds composed of a tamoxifen scaffold covalently bound to a ferrocene moiety, have shown very interesting antiproliferative, cytotoxic and immunologic effects. The formation of ferrocenyl quinone methide plays a crucial role in the multifaceted activity of ferrocifens. Lipid nanocapsules (LNCs), meanwhile, are nanoparticles obtained by a free organic solvent process. LNCs consist of an oily core surrounded by amphiphilic surfactants and are perfectly adapted to encapsulate these hydrophobic compounds. The different in vitro and in vivo experiments performed with this ferrocifen-loaded nanocarrier have revealed promising results in several multidrug-resistant cancer cell lines such as glioblastoma, breast cancer and metastatic melanoma, alone or in combination with other therapies. 

  • nanomedicine
  • bioorganometallic drug
  • cancer
  • lipid nanocapsule
  • ferrocifen
Please wait, diff process is still running!

References

  1. Uziely, B.; Jeffers, S.; Isacson, R.; Kutsch, K.; Wei-Tsao, D.; Yehoshua, Z.; Libson, E.; Muggia, F.M.; Gabizon, A. Liposomal Doxorubicin: Antitumor Activity and Unique Toxicities during Two Complementary Phase I Studies. J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol. 1995, 13, 1777–1785.
  2. Bobo, D.; Robinson, K.J.; Islam, J.; Thurecht, K.J.; Corrie, S.R. Nanoparticle-Based Medicines: A Review of FDA-Approved Materials and Clinical Trials to Date. Pharm. Res. 2016, 33, 2373–2387.
  3. Couvreur, P. Nanomedicine: From Where Are We Coming and Where Are We Going? J. Control. Release Off. J. Control. Release Soc. 2019, 311–312, 319–321.
  4. Reedijk, J. Platinum Anticancer Coordination Compounds: Study of DNA Binding Inspires New Drug Design. Eur. J. Inorg. Chem. 2009, 2009, 1303–1312.
  5. Al-Malky, H.S.; Al Harthi, S.E.; Osman, A.-M.M. Major Obstacles to Doxorubicin Therapy: Cardiotoxicity and Drug Resistance. J. Oncol. Pharm. Pract. Off. Publ. Int. Soc. Oncol. Pharm. Pract. 2020, 26, 434–444.
  6. Ali, S.; Rasool, M.; Chaoudhry, H.; N Pushparaj, P.; Jha, P.; Hafiz, A.; Mahfooz, M.; Abdus Sami, G.; Azhar Kamal, M.; Bashir, S.; et al. Molecular Mechanisms and Mode of Tamoxifen Resistance in Breast Cancer. Bioinformation 2016, 12, 135–139.
  7. Zhu, L.; Chen, L. Progress in Research on Paclitaxel and Tumor Immunotherapy. Cell. Mol. Biol. Lett. 2019, 24.
  8. Cao, Y.; Wei, Z.; Li, M.; Wang, H.; Yin, L.; Chen, D.; Wang, Y.; Chen, Y.; Yuan, Q.; Pu, X.; et al. Formulation, Pharmacokinetic Evaluation and Cytotoxicity of an Enhanced- Penetration Paclitaxel Nanosuspension. Curr. Cancer Drug Targets 2019, 19, 338–347.
  9. Jaouen, G.; Vessieres, A. Transition Metal Carbonyl Oestrogen Receptor Assay. Pure Appl. Chem. 1985, 57, 1865–1874.
  10. Jaouen, G.; Vessieres, A.; Top, S.; Ismail, A.A.; Butler, I.S. Metal Carbonyl Fragments as a New Class of Markers in Molecular Biology. J. Am. Chem. Soc. 1985, 107, 4778–4780.
  11. Hillard, E.; Vessières, A.; Le Bideau, F.; Plazuk, D.; Spera, D.; Huché, M.; Jaouen, G. A Series of Unconjugated Ferrocenyl Phenols: Prospects as Anticancer Agents. ChemMedChem 2006, 1, 551–559.
  12. Top, S.; Vessières, A.; Cabestaing, C.; Laios, I.; Leclercq, G.; Provot, C.; Jaouen, G. Studies on Organometallic Selective Estrogen Receptor Modulators. (SERMs) Dual Activity in the Hydroxy-Ferrocifen Series. J. Organomet. Chem. 2001, 637–639, 500–506.
  13. Vessières, A.; Top, S.; Beck, W.; Hillard, E.; Jaouen, G. Metal Complex SERMs (Selective Oestrogen Receptor Modulators). The Influence of Different Metal Units on Breast Cancer Cell Antiproliferative Effects. Dalton Trans. Camb. Engl. 2003 2006, 529–541.
  14. Maeda, H. Macromolecular Therapeutics in Cancer Treatment: The EPR Effect and Beyond. J. Control. Release Off. J. Control. Release Soc. 2012, 164, 138–144.
  15. Maeda, H. The 35th Anniversary of the Discovery of EPR Effect: A New Wave of Nanomedicines for Tumor-Targeted Drug Delivery-Personal Remarks and Future Prospects. J. Pers. Med. 2021, 11, 229.
  16. Danhier, F. To Exploit the Tumor Microenvironment: Since the EPR Effect Fails in the Clinic, What Is the Future of Nanomedicine? J. Control. Release Off. J. Control. Release Soc. 2016, 244, 108–121.
  17. Sindhwani, S.; Syed, A.M.; Ngai, J.; Kingston, B.R.; Maiorino, L.; Rothschild, J.; MacMillan, P.; Zhang, Y.; Rajesh, N.U.; Hoang, T.; et al. The Entry of Nanoparticles into Solid Tumours. Nat. Mater. 2020, 19, 566–575.
  18. Poste, G.; Kirsh, R. Site–Specific (Targeted) Drug Delivery in Cancer Therapy. Bio/Technology 1983, 1, 869–878.
  19. Rolland, A.; Bourel, D.; Genetet, B.; Le Verge, R. Monoclonal Antibodies Covalently Coupled to Polymethacrylic Nanoparticles: In Vitro Specific Targeting to Human T Lymphocytes. Int. J. Pharm. 1987, 39, 173–180.
  20. Barbet, J.; Machy, P.; Leserman, L.D. Monoclonal Antibody Covalently Coupled to Liposomes: Specific Targeting to Cells. J. Supramol. Struct. Cell. Biochem. 1981, 16, 243–258.
  21. Hirsjärvi, S.; Passirani, C.; Benoit, J.-P. Passive and Active Tumour Targeting with Nanocarriers. Curr. Drug Discov. Technol. 2011, 8, 188–196.
  22. Clemons, T.D.; Singh, R.; Sorolla, A.; Chaudhari, N.; Hubbard, A.; Iyer, K.S. Distinction Between Active and Passive Targeting of Nanoparticles Dictate Their Overall Therapeutic Efficacy. Langmuir ACS J. Surf. Colloids 2018, 34, 15343–15349.
  23. Attia, M.F.; Anton, N.; Wallyn, J.; Omran, Z.; Vandamme, T.F. An Overview of Active and Passive Targeting Strategies to Improve the Nanocarriers Efficiency to Tumour Sites. J. Pharm. Pharmacol. 2019, 71, 1185–1198.
  24. Heurtault, B.; Saulnier, P.; Pech, B.; Proust, J.-E.; Benoit, J.-P. A Novel Phase Inversion-Based Process for the Preparation of Lipid Nanocarriers. Pharm. Res. 2002, 19, 875–880.
  25. Heurtault, B.; Saulnier, P.; Benoit, J.-P.; Proust, J.-E.; Pech, B.; Richard, J. Lipid Nanocapsules, Preparation Process and Use as Medicine. U.S. Patent 8057823B2, 15 November 2011. Available online: (accessed on 17 April 2020).
  26. Béduneau, A.; Hindré, F.; Clavreul, A.; Leroux, J.-C.; Saulnier, P.; Benoit, J.-P. Brain Targeting Using Novel Lipid Nanovectors. J. Control. Release Off. J. Control. Release Soc. 2008, 126, 44–49.
  27. Roger, E.; Lagarce, F.; Garcion, E.; Benoit, J.-P. Lipid Nanocarriers Improve Paclitaxel Transport throughout Human Intestinal Epithelial Cells by Using Vesicle-Mediated Transcytosis. J. Control. Release Off. J. Control. Release Soc. 2009, 140, 174–181.
  28. Laine, A.-L.; Huynh, N.T.; Clavreul, A.; Balzeau, J.; Béjaud, J.; Vessieres, A.; Benoit, J.-P.; Eyer, J.; Passirani, C. Brain Tumour Targeting Strategies via Coated Ferrociphenol Lipid Nanocapsules. Eur. J. Pharm. Biopharm. Off. J. Arbeitsgemeinschaft Pharm. Verfahrenstechnik EV 2012, 81, 690–693.
  29. Balzeau, J.; Pinier, M.; Berges, R.; Saulnier, P.; Benoit, J.-P.; Eyer, J. The Effect of Functionalizing Lipid Nanocapsules with NFL-TBS.40-63 Peptide on Their Uptake by Glioblastoma Cells. Biomaterials 2013, 34, 3381–3389.
  30. Carradori, D.; Saulnier, P.; Préat, V.; des Rieux, A.; Eyer, J. NFL-Lipid Nanocapsules for Brain Neural Stem Cell Targeting in Vitro and in Vivo. J. Control. Release Off. J. Control. Release Soc. 2016, 238, 253–262.
  31. David, S.; Montier, T.; Carmoy, N.; Resnier, P.; Clavreul, A.; Mével, M.; Pitard, B.; Benoit, J.-P.; Passirani, C. Treatment Efficacy of DNA Lipid Nanocapsules and DNA Multimodular Systems after Systemic Administration in a Human Glioma Model. J. Gene Med. 2012, 14, 769–775.
  32. Allard, E.; Hindré, F.; Passirani, C.; Lemaire, L.; Lepareur, N.; Noiret, N.; Menei, P.; Benoit, J.-P. 188Re-Loaded Lipid Nanocapsules as a Promising Radiopharmaceutical Carrier for Internal Radiotherapy of Malignant Gliomas. Eur. J. Nucl. Med. Mol. Imaging 2008, 35, 1838–1846.
  33. Heurtault, B.; Saulnier, P.; Pech, B.; Venier-Julienne, M.-C.; Proust, J.-E.; Phan-Tan-Luu, R.; Benoît, J.-P. The Influence of Lipid Nanocapsule Composition on Their Size Distribution. Eur. J. Pharm. Sci. Off. J. Eur. Fed. Pharm. Sci. 2003, 18, 55–61.
  34. Shinoda, K.; Saito, H. The Stability of O/W Type Emulsions as Functions of Temperature and the HLB of Emulsifiers: The Emulsification by PIT-Method. J. Colloid Interface Sci. 1969, 30, 258–263.
  35. Anton, N.; Gayet, P.; Benoit, J.-P.; Saulnier, P. Nano-Emulsions and Nanocapsules by the PIT Method: An Investigation on the Role of the Temperature Cycling on the Emulsion Phase Inversion. Int. J. Pharm. 2007, 344, 44–52.
  36. Garcion, E.; Lamprecht, A.; Heurtault, B.; Paillard, A.; Aubert-Pouessel, A.; Denizot, B.; Menei, P.; Benoît, J.-P. A New Generation of Anticancer, Drug-Loaded, Colloidal Vectors Reverses Multidrug Resistance in Glioma and Reduces Tumor Progression in Rats. Mol. Cancer Ther. 2006, 5, 1710–1722.
  37. Heurtault, B.; Saulnier, P.; Pech, B.; Benoît, J.P.; Proust, J. Interfacial Stability of Lipid Nanocapsules. Colloids Surf. B Biointerfaces 2003, 30, 225–235.
  38. Vu, V.P.; Gifford, G.B.; Chen, F.; Benasutti, H.; Wang, G.; Groman, E.V.; Scheinman, R.; Saba, L.; Moghimi, S.M.; Simberg, D. Immunoglobulin Deposition on Biomolecule Corona Determines Complement Opsonization Efficiency of Preclinical and Clinical Nanoparticles. Nat. Nanotechnol. 2019, 14, 260–268.
  39. Afshar-Kharghan, V. The Role of the Complement System in Cancer. J. Clin. Investig. 2017, 127, 780–789.
  40. Passirani, C.; Barratt, G.; Devissaguet, J.P.; Labarre, D. Interactions of Nanoparticles Bearing Heparin or Dextran Covalently Bound to Poly(Methyl Methacrylate) with the Complement System. Life Sci. 1998, 62, 775–785.
  41. Knop, K.; Hoogenboom, R.; Fischer, D.; Schubert, U.S. Poly(Ethylene Glycol) in Drug Delivery: Pros and Cons as Well as Potential Alternatives. Angew. Chem. Int. Ed. Engl. 2010, 49, 6288–6308.
  42. Béduneau, A.; Saulnier, P.; Anton, N.; Hindré, F.; Passirani, C.; Rajerison, H.; Noiret, N.; Benoit, J.-P. Pegylated Nanocapsules Produced by an Organic Solvent-Free Method: Evaluation of Their Stealth Properties. Pharm. Res. 2006, 23, 2190–2199.
  43. Lainé, A.-L.; Gravier, J.; Henry, M.; Sancey, L.; Béjaud, J.; Pancani, E.; Wiber, M.; Texier, I.; Coll, J.-L.; Benoit, J.-P.; et al. Conventional versus Stealth Lipid Nanoparticles: Formulation and in Vivo Fate Prediction through FRET Monitoring. J. Control. Release Off. J. Control. Release Soc. 2014, 188, 1–8.
  44. Perrier, T.; Saulnier, P.; Fouchet, F.; Lautram, N.; Benoît, J.-P. Post-Insertion into Lipid NanoCapsules (LNCs): From Experimental Aspects to Mechanisms. Int. J. Pharm. 2010, 396, 204–209.
  45. Resnier, P.; LeQuinio, P.; Lautram, N.; André, E.; Gaillard, C.; Bastiat, G.; Benoit, J.-P.; Passirani, C. Efficient in Vitro Gene Therapy with PEG SiRNA Lipid Nanocapsules for Passive Targeting Strategy in Melanoma. Biotechnol. J. 2014, 9, 1389–1401.
  46. Vonarbourg, A.; Passirani, C.; Saulnier, P.; Simard, P.; Leroux, J.C.; Benoit, J.P. Evaluation of Pegylated Lipid Nanocapsules versus Complement System Activation and Macrophage Uptake. J. Biomed. Mater. Res. A 2006, 78, 620–628.
  47. Thakur, S.; Kesharwani, P.; Tekade, R.K.; Jain, N.K. Impact of Pegylation on Biopharmaceutical Properties of Dendrimers. Polymer 2015, 59, 67–92.
  48. Huynh, N.T.; Morille, M.; Bejaud, J.; Legras, P.; Vessieres, A.; Jaouen, G.; Benoit, J.-P.; Passirani, C. Treatment of 9L Gliosarcoma in Rats by Ferrociphenol-Loaded Lipid Nanocapsules Based on a Passive Targeting Strategy via the EPR Effect. Pharm. Res. 2011, 28, 3189–3198.
  49. Morille, M.; Montier, T.; Legras, P.; Carmoy, N.; Brodin, P.; Pitard, B.; Benoît, J.-P.; Passirani, C. Long-Circulating DNA Lipid Nanocapsules as New Vector for Passive Tumor Targeting. Biomaterials 2010, 31, 321–329.
  50. Pasut, G.; Veronese, F.M. State of the Art in PEGylation: The Great Versatility Achieved after Forty Years of Research. J. Control. Release Off. J. Control. Release Soc. 2012, 161, 461–472.
  51. Béduneau, A.; Saulnier, P.; Hindré, F.; Clavreul, A.; Leroux, J.-C.; Benoit, J.-P. Design of Targeted Lipid Nanocapsules by Conjugation of Whole Antibodies and Antibody Fab’ Fragments. Biomaterials 2007, 28, 4978–4990.
  52. Resnier, P.; Lepeltier, E.; Emina, A.L.; Galopin, N.; Bejaud, J.; David, S.; Ballet, C.; Benvegnu, T.; Pecorari, F.; Chourpa, I.; et al. Model Affitin and PEG Modifications onto SiRNA Lipid Nanocapsules: Cell Uptake and in Vivo Biodistribution Improvements. RSC Adv. 2019, 9, 27264–27278.
  53. Benoit, J.-P.; Perrier, T. Method for Preparing Functionalized Lipid Capsules. U.S. Patent 9333181B2, 5 October 2016. Available online: (accessed on 9 June 2020).
  54. Bechara, C.; Sagan, S. Cell-Penetrating Peptides: 20 Years Later, Where Do We Stand? FEBS Lett. 2013, 587, 1693–1702.
  55. Karim, R.; Lepeltier, E.; Esnault, L.; Pigeon, P.; Lemaire, L.; Lépinoux-Chambaud, C.; Clere, N.; Jaouen, G.; Eyer, J.; Piel, G.; et al. Enhanced and Preferential Internalization of Lipid Nanocapsules into Human Glioblastoma Cells: Effect of a Surface-Functionalizing NFL Peptide. Nanoscale 2018, 10, 13485–13501.
  56. Lainé, A.-L.; Adriaenssens, E.; Vessières, A.; Jaouen, G.; Corbet, C.; Desruelles, E.; Pigeon, P.; Toillon, R.-A.; Passirani, C. The in Vivo Performance of Ferrocenyl Tamoxifen Lipid Nanocapsules in Xenografted Triple Negative Breast Cancer. Biomaterials 2013, 34, 6949–6956.
  57. Resnier, P.; Galopin, N.; Sibiril, Y.; Clavreul, A.; Cayon, J.; Briganti, A.; Legras, P.; Vessières, A.; Montier, T.; Jaouen, G.; et al. Efficient Ferrocifen Anticancer Drug and Bcl-2 Gene Therapy Using Lipid Nanocapsules on Human Melanoma Xenograft in Mouse. Pharmacol. Res. 2017, 126, 54–65.
  58. Topin-Ruiz, S.; Mellinger, A.; Lepeltier, E.; Bourreau, C.; Fouillet, J.; Riou, J.; Jaouen, G.; Martin, L.; Passirani, C.; Clere, N. P722 Ferrocifen Loaded Lipid Nanocapsules Improve Survival of Murine Xenografted-Melanoma via a Potentiation of Apoptosis and an Activation of CD8+ T Lymphocytes. Int. J. Pharm. 2021, 593, 120111.
  59. Vessières, A.; Corbet, C.; Heldt, J.M.; Lories, N.; Jouy, N.; Laïos, I.; Leclercq, G.; Jaouen, G.; Toillon, R.-A. A Ferrocenyl Derivative of Hydroxytamoxifen Elicits an Estrogen Receptor-Independent Mechanism of Action in Breast Cancer Cell Lines. J. Inorg. Biochem. 2010, 104, 503–511.
  60. Michard, Q.; Jaouen, G.; Vessieres, A.; Bernard, B.A. Evaluation of Cytotoxic Properties of Organometallic Ferrocifens on Melanocytes, Primary and Metastatic Melanoma Cell Lines. J. Inorg. Biochem. 2008, 102, 1980–1985.
  61. Allard, E.; Passirani, C.; Garcion, E.; Pigeon, P.; Vessières, A.; Jaouen, G.; Benoit, J.-P. Lipid Nanocapsules Loaded with an Organometallic Tamoxifen Derivative as a Novel Drug-Carrier System for Experimental Malignant Gliomas. J. Control. Release Off. J. Control. Release Soc. 2008, 130, 146–153.
  62. Allard, E.; Jarnet, D.; Vessières, A.; Vinchon-Petit, S.; Jaouen, G.; Benoit, J.-P.; Passirani, C. Local Delivery of Ferrociphenol Lipid Nanocapsules Followed by External Radiotherapy as a Synergistic Treatment against Intracranial 9L Glioma Xenograft. Pharm. Res. 2010, 27, 56–64.
  63. Huynh, N.T.; Passirani, C.; Allard-Vannier, E.; Lemaire, L.; Roux, J.; Garcion, E.; Vessieres, A.; Benoit, J.-P. Administration-Dependent Efficacy of Ferrociphenol Lipid Nanocapsules for the Treatment of Intracranial 9L Rat Gliosarcoma. Int. J. Pharm. 2012, 423, 55–62.
  64. Roger, M.; Clavreul, A.; Huynh, N.T.; Passirani, C.; Schiller, P.; Vessières, A.; Montero-Menei, C.; Menei, P. Ferrociphenol Lipid Nanocapsule Delivery by Mesenchymal Stromal Cells in Brain Tumor Therapy. Int. J. Pharm. 2012, 423, 63–68.
  65. Clavreul, A.; Montagu, A.; Lainé, A.-L.; Tétaud, C.; Lautram, N.; Franconi, F.; Passirani, C.; Vessières, A.; Montero-Menei, C.N.; Menei, P. Targeting and Treatment of Glioblastomas with Human Mesenchymal Stem Cells Carrying Ferrociphenol Lipid Nanocapsules. Int. J. Nanomed. 2015, 10, 1259–1271.
  66. Lainé, A.-L.; Clavreul, A.; Rousseau, A.; Tétaud, C.; Vessieres, A.; Garcion, E.; Jaouen, G.; Aubert, L.; Guilbert, M.; Benoit, J.-P.; et al. Inhibition of Ectopic Glioma Tumor Growth by a Potent Ferrocenyl Drug Loaded into Stealth Lipid Nanocapsules. Nanomed. Nanotechnol. Biol. Med. 2014, 10, 1667–1677.
  67. Omuro, A.; DeAngelis, L.M. Glioblastoma and Other Malignant Gliomas: A Clinical Review. JAMA 2013, 310, 1842–1850.
  68. Vinchon-Petit, S.; Jarnet, D.; Paillard, A.; Benoit, J.-P.; Garcion, E.; Menei, P. In Vivo Evaluation of Intracellular Drug-Nanocarriers Infused into Intracranial Tumours by Convection-Enhanced Delivery: Distribution and Radiosensitisation Efficacy. J. Neurooncol. 2010, 97, 195–205.
  69. Allard, E.; Passirani, C.; Benoit, J.-P. Convection-Enhanced Delivery of Nanocarriers for the Treatment of Brain Tumors. Biomaterials 2009, 30, 2302–2318.
  70. MacKay, J.A.; Deen, D.F.; Szoka, F.C. Distribution in Brain of Liposomes after Convection Enhanced Delivery; Modulation by Particle Charge, Particle Diameter, and Presence of Steric Coating. Brain Res. 2005, 1035, 139–153.
  71. Ishida, T.; Kiwada, H. Accelerated Blood Clearance (ABC) Phenomenon upon Repeated Injection of PEGylated Liposomes. Int. J. Pharm. 2008, 354, 56–62.
  72. Zhao, J.; Qin, Z.; Wu, J.; Li, L.; Jin, Q.; Ji, J. Zwitterionic Stealth Peptide-Protected Gold Nanoparticles Enable Long Circulation without the Accelerated Blood Clearance Phenomenon. Biomater. Sci. 2017, 6, 200–206.
  73. Bruyère, C.; Mathieu, V.; Vessières, A.; Pigeon, P.; Top, S.; Jaouen, G.; Kiss, R. Ferrocifen Derivatives That Induce Senescence in Cancer Cells: Selected Examples. J. Inorg. Biochem. 2014, 141, 144–151.
  74. Sun, Y.-S.; Zhao, Z.; Yang, Z.-N.; Xu, F.; Lu, H.-J.; Zhu, Z.-Y.; Shi, W.; Jiang, J.; Yao, P.-P.; Zhu, H.-P. Risk Factors and Preventions of Breast Cancer. Int. J. Biol. Sci. 2017, 13, 1387–1397.
  75. Scully, O.J.; Bay, B.-H.; Yip, G.; Yu, Y. Breast Cancer Metastasis. Cancer Genomics Proteomics 2012, 9, 311–320.
  76. Yang, Y.; Pan, W.; Tang, X.; Wu, S.; Sun, X. A Meta-Analysis of Randomized Controlled Trials Comparing the Efficacy and Safety of Anastrozole versus Tamoxifen for Breast Cancer. Oncotarget 2017, 8, 48362–48374.
  77. Pautu, V.; Leonetti, D.; Lepeltier, E.; Clere, N.; Passirani, C. Nanomedicine as a Potent Strategy in Melanoma Tumor Microenvironment. Pharmacol. Res. 2017, 126, 31–53.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)
Feedback