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 i n 90% of both Ewing's sarcoma and primitive neuroectodermal tumor (PNET). I n the present study, we show that recently developed polyisobutylcyanoacryl ate nanocapsules with an aqueous core were able to encapsulate efficiently high amounts of phosphorothioate oligonucleotides (ODN) directed against EW S 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 a ble 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 sa rcoma-related tumor in mice after intratumoral injection of a cumulative do se as low as 14.4 nanomoles. This new type of non viral vector shows great potential for in vivo administration of oligonucleotides. (C) 2000 Academic Press.