Inhibition of ectopic glioma tumor growth by a potent ferrocenyl drug loaded into stealth lipid nanocapsules.
In this work, a novel ferrocenyl complex (ansa-FcdiOH) was assessed for brain tumor therapy through stealth lipid nanocapsules (LNCs). Stealth LNCs, prepared according to a one-step process, showed rapid uptake by cancer cells and extended blood circulation time. The ferrocenyl complex was successfully encapsulated into these LNCs measuring 40 nm with a high loading capacity (6.4%). In vitro studies showed a potent anticancer effect of ansa-FcdiOH on 9L cells with a low IC50 value (0.1 μM) associated with an oxidative stress and a dose-dependent alteration of the cell cycle. Repeated intravenous injections of stealth ansa-FcdiOH LNCs in ectopic glioma bearing rats induced a significant tumor growth inhibition, supported by a reduced number of proliferative cells in tumors compared to control group. Additionally, no liver damage was observed in treated animals. These results indicated that stealth ansa-FcdiOH LNCs might be considered as a potential new approach for cancer chemotherapy.


BACKGROUND
In this study, a novel ferrocenyl complex was assessed for brain tumor therapy through stealth lipid nanocapsules, demonstrating no liver damage, and superior tumor volume reduction compared to saline and stealth lipid nanocapsules alone in an ectopic glioma model.
LUNAM Université - Micro et Nanomédecines Biomimétiques, Angers, France; Inserm U1066, IBS-CHU, Angers, France.
Anne-Laure
AL
Lainé
Inserm U1066, IBS-CHU, Angers, France; Département de Neurochirurgie - CHU, Angers, France.
Anne
A
Clavreul
Département de Pathologie Cellulaire et Tissulaire - CHU, Angers, France.
Audrey
A
Rousseau
Inserm U1066, IBS-CHU, Angers, France; Département de Neurochirurgie - CHU, Angers, France.
Clément
C
Tétaud
CNRS, UMR 7576, ENSCP, Paris, France.
Anne
A
Vessieres
LUNAM Université - Micro et Nanomédecines Biomimétiques, Angers, France; Inserm U1066, IBS-CHU, Angers, France.
Emmanuel
E
Garcion
CNRS, UMR 7576, ENSCP, Paris, France.
Gerard
G
Jaouen
Inserm U908, Université Lille 1, Villeneuve d'Ascq, France.
Léo
L
Aubert
Inserm U908, Université Lille 1, Villeneuve d'Ascq, France.
Matthieu
M
Guilbert
LUNAM Université - Micro et Nanomédecines Biomimétiques, Angers, France; Inserm U1066, IBS-CHU, Angers, France.
Jean-Pierre
JP
Benoit
Inserm U908, Université Lille 1, Villeneuve d'Ascq, France.
Robert-Alain
RA
Toillon
LUNAM Université - Micro et Nanomédecines Biomimétiques, Angers, France; Inserm U1066, IBS-CHU, Angers, France. Electronic address: Catherine.passirani@univ-angers.fr.
Catherine
C
Passirani
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry; D005260:Female; D005296:Ferrous Compounds / Q000737:chemistry* / Q000627:therapeutic use*; D005910:Glioma / Q000188:drug therapy*; D053769:Nanocapsules / Q000737:chemistry*; D050997:Nanomedicine; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species
D004337:Drug Carriers; D005296:Ferrous Compounds; D053769:Nanocapsules; D017382:Reactive Oxygen Species
Cell cycle; EPR effect; Nanomedicine; ansa-FcdiOH