Imaged-guided Therapy of Ewing Sarcoma Using targeting Nanoparticles encapsulated with Iron oxide and siRNA against EWS/FLI1

Ewing Sarcoma (ES) is the second most common bone tumor in children and adolescents. It is characterized by a specific translocation between the EWS gene and members of the ETS-family of transcription factors. The reciprocal translocation between EWS and FLI1 [t(11;22)(q24;q12)] is identified in about 86% of ES. Furthermore tumor cells strongly express the CD99 surface antigen and the Ewing Tumor-Associated Antigen (ETAA). The objective of the project is to deliver siRNA against EWS/FLI1 using magnetic nanoparticles for monitoring of delivery via MRI. Coupling of respective particles with an anti-CD99 and/or an anti-ETAA antibody will allow specific targeting and uptake into ES cells. Therefore iron oxide nanoparticles and siRNA will be (co-) encapsulated into liposomes, functionalized with targeting antibodies to allow delivery of siRNA and iron particles. We could show that coupling of antibodies to conventional SPC/Chol liposomes and to functionalized liposomes allow specific detection of ES cells (TC-71 and CHP-100) followed by internalization via receptor mediated endocytosis. The next step is to validate the encapsulation of siRNA and iron oxide into targeting Lipid-Protamin-siRNA particles (LPR).