title: Targeting and treatment of glioblastomas with human mesenchymal stem cells carrying ferrociphenol lipid nanocapsules.
abstract: Recently developed drug delivery nanosystems, such as lipid nanocapsules (LNCs), hold great promise for the treatment of glioblastomas (GBs). In this study, we used a subpopulation of human mesenchymal stem cells, "marrow-isolated adult multilineage inducible" (MIAMI) cells, which have endogenous tumor-homing activity, to deliver LNCs containing an organometallic complex (ferrociphenol or Fc-diOH), in the orthotopic U87MG GB model. We determined the optimal dose of Fc-diOH-LNCs that can be carried by MIAMI cells and compared the efficacy of Fc-diOH-LNC-loaded MIAMI cells with that of the free-standing Fc-diOH-LNC system. We showed that MIAMI cells entrapped an optimal dose of about 20 pg Fc-diOH per cell, with no effect on cell viability or migration capacity. The survival of U87MG-bearing mice was longer after the intratumoral injection of Fc-diOH-LNC-loaded MIAMI cells than after the injection of Fc-diOH-LNCs alone. The greater effect of the Fc-diOH-LNC-loaded MIAMI cells may be accounted for by their peritumoral distribution and a longer residence time of the drug within the tumor. These results confirm the potential of combinations of stem cell therapy and nanotechnology to improve the local tissue distribution of anticancer drugs in GB.
authors.affiliation: Département de Neurochirurgie, Centre Hospitalier Universitaire, Angers, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Clavreul
authors.affiliation: INSERM UMR-S 1066, Université d'Angers, LUNAM Université, Angers, France.
authors.forename: Angélique
authors.initials: A
authors.lastname: Montagu
authors.affiliation: INSERM UMR-S 1066, Université d'Angers, LUNAM Université, Angers, France.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Lainé
authors.affiliation: INSERM UMR-S 1066, Université d'Angers, LUNAM Université, Angers, France.
authors.forename: Clément
authors.initials: C
authors.lastname: Tétaud
authors.affiliation: INSERM UMR-S 1066, Université d'Angers, LUNAM Université, Angers, France.
authors.forename: Nolwenn
authors.initials: N
authors.lastname: Lautram
authors.affiliation: CIFAB-PRIMEX, Université d'Angers, LUNAM Université, Angers, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Franconi
authors.affiliation: INSERM UMR-S 1066, Université d'Angers, LUNAM Université, Angers, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Passirani
authors.affiliation: CNRS-UMR 7223, ENSCP, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Vessières
authors.affiliation: INSERM UMR-S 1066, Université d'Angers, LUNAM Université, Angers, France.
authors.forename: Claudia N
authors.initials: CN
authors.lastname: Montero-Menei
authors.affiliation: Département de Neurochirurgie, Centre Hospitalier Universitaire, Angers, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Menei
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005296:Ferrous Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D005909:Glioblastoma / Q000628:therapy*; D006801:Humans; D008055:Lipids / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D045164:Mesenchymal Stem Cell Transplantation; D051379:Mice; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D005296:Ferrous Compounds; D008055:Lipids; D053769:Nanocapsules; C533771:ferrociphenol
keywords: drug delivery; glioblastoma; mesenchymal stem cells; nanoparticle; targeting