title: Ferrociphenol lipid nanocapsule delivery by mesenchymal stromal cells in brain tumor therapy.
abstract: The prognosis of patients with malignant glioma remains extremely poor despite surgery and improvements in radio- and chemo-therapies. Thus, treatment strategies that specifically target these tumors have the potential to greatly improve therapeutic outcomes. "Marrow-isolated adult multilineage inducible" cells (MIAMI cells) are a subpopulation of mesenchymal stromal cells (MSCs) which possess the ability to migrate to brain tumors. We have previously shown that MIAMI cells were able to efficiently incorporate lipid nanocapsules (LNCs) without altering either their stem cell properties or their migration capacity. In this study, we assessed whether the cytotoxic effects of MIAMI cells loaded with LNCs containing an organometallic complex (ferrociphenol or Fc-diOH) could be used to treat brain tumors. The results showed that MIAMI cells internalized Fc-diOH-LNCs and that this internalization did not induce MIAMI cell death. Furthermore, Fc-diOH-LNC-loaded MIAMI cells produced a cytotoxic effect on U87MG glioma cells in vitro. This cytotoxic effect was validated in vivo after intratumoral injection of Fc-diOH-LNC-loaded MIAMI cells in a heterotopic U87MG glioma model in nude mice. These promising results open up a new field of treatment in which cellular vehicles and nanoparticles can be combined to treat brain tumors.
authors.affiliation: LUNAM Université, Ingénierie de la Vectorisation Particulaire, F-49933 Angers, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Roger
authors.forename: Anne
authors.initials: A
authors.lastname: Clavreul
authors.forename: Ngoc Trinh
authors.initials: NT
authors.lastname: Huynh
authors.forename: Catherine
authors.initials: C
authors.lastname: Passirani
authors.forename: Paul
authors.initials: P
authors.lastname: Schiller
authors.forename: Anne
authors.initials: A
authors.lastname: Vessières
authors.forename: Claudia
authors.initials: C
authors.lastname: Montero-Menei
authors.forename: Philippe
authors.initials: P
authors.lastname: Menei
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018920:Coculture Techniques; D003374:Coumarins / Q000008:administration & dosage / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D005296:Ferrous Compounds / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D005909:Glioblastoma / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D015552:Injections, Intralesional; D008055:Lipids / Q000737:chemistry*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D053769:Nanocapsules / Q000737:chemistry*; D010316:Particle Size; D037121:Plant Lectins / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D030262:Soybean Proteins / Q000737:chemistry; D055672:Static Electricity; D013229:Stearic Acids / Q000737:chemistry; D013844:Thiazoles / Q000008:administration & dosage / Q000378:metabolism; D016896:Treatment Outcome; D014280:Triglycerides / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays; D010835:Phytohemagglutinins
chemical_list: D000970:Antineoplastic Agents; D003374:Coumarins; D005296:Ferrous Compounds; D008055:Lipids; D053769:Nanocapsules; D037121:Plant Lectins; D011092:Polyethylene Glycols; D030262:Soybean Proteins; D013229:Stearic Acids; D013844:Thiazoles; D014280:Triglycerides; C517282:coumarin 6; C533771:ferrociphenol; C028824:soybean lectin; D010835:Phytohemagglutinins; C067028:Solutol HS 15