PRO-DRUG NANOPARTICLES AS SYNERGISTIC DRUG COMBINATION CARRIERS FOR IDH1-WT GLIOBLASTOMA

Abstract AIMS Synergistic combinations of doxorubicin and gemcitabine have been assessed for post-surgical treatment IDH1 wild-type glioblastoma (GBM). As a complementary drug carrier, hyperbranched micellar nanoparticles are being investigated to enable enhanced loading sustained release. METHOD 2D 3D spheroid in vitro models generated from patient-derived cells resected tumour core invasive margin. Drug were screened using synergy quantification the Chou Talalay method mechanisms measures caspase 3/6-mediated apoptosis γH2AX-mediated DNA damage. Polymeric (PEG-PCL) loaded with Cy5 tested internalisation subsequent endocytosis pathway determination. Both single currently incorporated into PEG-PCL assessment biocompatibility, cellular uptake cytotoxicity. RESULTS Data demonstrate synergism is obtained molar ratio de- pendent manner. Consistent this, damage observed synergistic effcient internalised via dynamin-dependent caveolae clathrin endocytotic pathways. Interestingly, nanoparticle substantially in- creased (approx. 50%) GBM relative proliferative cells. CONCLUSIONS Doxorubicin has identified as combination potential release when combined formulations. Together, data provided platform knowledge that will translation pre-clinical vivo models.