EWS fli-1 antisense nanocapsules inhibits ewing sarcoma-related tumor in mice.
EWS Fli-1, a fusion gene resulting from a t(11;22) translocation is found in 90% of both Ewing's sarcoma and primitive neuroectodermal tumor (PNET). In the present study, we show that recently developed polyisobutylcyanoacrylate nanocapsules with an aqueous core were able to encapsulate efficiently high amounts of phosphorothioate oligonucleotides (ODN) directed against EWS Fli-1 chimeric RNA. Release of these ODN in serum medium was shown to be biphasic which was explained by the presence of two types of nanocapsules able to release ODN with different kinetics. In addition, nanocapsules were found to provide protection of these oligonucleotides from the degradation in serum. These ODN nanocapsules permitted to obtain inhibition of Ewing sarcoma-related tumor in mice after intratumoral injection of a cumulative dose as low as 14.4 nanomoles. This new type of non viral vector shows great potential for in vivo administration of oligonucleotides.
Lambert
G
G
Laboratoire de physico-chimie, UMR CNRS 8612, Châtenay-Malabry, France.
Bertrand
J R
JR
Fattal
E
E
Subra
F
F
Pinto-Alphandary
H
H
Malvy
C
C
Auclair
C
C
Couvreur
P
P
D016475:3T3 Cells; D000818:Animals; D002214:Capsules; D004268:DNA-Binding Proteins / Q000235:genetics*; D004337:Drug Carriers; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D018242:Neuroectodermal Tumors, Primitive / Q000235:genetics; D020319:Oligodeoxyribonucleotides, Antisense / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D051789:Proto-Oncogene Protein c-fli-1; D011518:Proto-Oncogene Proteins; D012512:Sarcoma, Ewing / Q000235:genetics* / Q000628:therapy*; D013873:Thionucleotides; D015534:Trans-Activators / Q000235:genetics*; D014162:Transfection
D002214:Capsules; D004268:DNA-Binding Proteins; D004337:Drug Carriers; C497426:Fli1 protein, mouse; D020319:Oligodeoxyribonucleotides, Antisense; D051789:Proto-Oncogene Protein c-fli-1; D011518:Proto-Oncogene Proteins; D013873:Thionucleotides; D015534:Trans-Activators