Imaged-guided Therapy of Ewing Sarcoma Using Magnetic Nanoparticles Coupled with anti-CD99-Antibody 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. 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 allow specific detection of ES cells (TC-71 and CHP-100) followed by internalization via receptor mediated endocytosis. The next step is to encapsulate iron particles into liposomes coupled with targeting antibodies and visualize the in vitro uptake via MRI.