Local delivery of ferrociphenol lipid nanocapsules followed by external radiotherapy as a synergistic treatment against intracranial 9L glioma xenograft.
OBJECTIVE
The goal of the present study was to evaluate the efficacy of a new organometallic drug, ferrociphenol (Fc-diOH), in combination with external radiotherapy in intracerebral 9L glioma model. We tested the hypothesis that the combination of external radiotherapy with Fc-diOH could potentiate the action of this drug.


METHODS
9L cells were treated with Fc-diOH-LNCs (from 0.01 to 1 micromol/L) and irradiated with external radiotherapy (from 2 to 40 Gy). In vivo assessment was evaluated by the inoculation of 9L cells in Fisher rats. Chemotherapy with Fc-diOH-LNCs (0.36 mg/rat) was administered by means of convection-enhanced delivery (CED), and the treatment was followed by three irradiations of 6 Gy doses (total dose = 18 Gy).


RESULTS
In vitro evaluations evidenced that a combined treatment with Fc-diOH-LNCs and irradiations showed synergistic antitumor activity on 9L cells. Combining cerebral irradiation with CED of Fc-diOH-LNCs led to a significantly longer survival and the existence of long-term survivors compared to Fc-diOH-LNCs-treated animals (p < 0.0001) and to the group treated with blank LNCs + radiotherapy (p = 0.0079).


CONCLUSIONS
The synergistic effect between ferrociphenol-loaded LNCs and radiotherapy was due to a closely oxidative relationship. Upon these considerations, Fc-diOH-LNCs appear to be an efficient radiosensitive anticancer drug delivery system.
Allard
Emilie
E
Inserm U646, Pôle pharmaceutique, CHU d'Angers, Université d'Angers, 49100, Angers, France.
Jarnet
Delphine
D
Vessières
Anne
A
Vinchon-Petit
Sandrine
S
Jaouen
Gérard
G
Benoit
Jean-Pierre
JP
Passirani
Catherine
C
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003131:Combined Modality Therapy / Q000379:methods; D016371:Cranial Irradiation / Q000379:methods*; D005260:Female; D005296:Ferrous Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D005910:Glioma / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy; D036502:Infusions, Intralesional; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D051381:Rats; D011916:Rats, Inbred F344; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D005296:Ferrous Compounds; D053769:Nanocapsules; C533771:ferrociphenol