Small rigid platforms functionalization with quaternary ammonium: Targeting extracellular matrix of chondrosarcoma

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Miot-Noirault, Elisabeth | Vidal, Aurélien | Morlieras, Jessica | Bonazza, Pauline | Auzeloux, Philippe | Besse, Sophie | Dauplat, Marie-Mélanie | Peyrode, Caroline | Degoul, Françoise | Billotey, Claire | Lux, François | Rédini, Françoise | Tillement, Olivier | Chezal, Jean-Michel | Kryza, David | Janier, Marc

Edité par CCSD ; Elsevier -

International audience. This work takes place in the “cartilage targeting strategy”, consisting in using the quaternary ammonium (QA) function as a vector to proteoglycans (PGs) of extracellular matrix (ECM). The objective was to demonstrate that QA could address gadolinium based small rigid platforms (SRP) to PG-rich tumors. SRP were functionalized with QA, radiolabeled with 111Indium and evaluated for biodistribution in vivo, respectively to non functionalized SRP, in two experimental models: (i) the HEMCSS human xenograft model; (ii) the Swarm rat chondrosarcoma (SRC) orthotopic model. The contribution of cellular uptake to tumoral accumulation of nano-objects was also determined from in vitro binding. In the SRC model expressing a highly and homogeneously distributed PG content, tumor accumulation and retention of SRP@QA were increased by 40% as compared to non-functionalized SRP. When considering the radiosensitizing potential of gadolinium based SRP, these results provide hopes for the radiobiological approach of highly resistant tumor such as chondrosarcoma.

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