DDEL-17. POOLED CANCER CELL SCREENING IDENTIFIES GENOMIC DETERMINANTS OF NANOPARTICLE DELIVERY TO CANCER CELLS: SUB ANALYSIS OF CENTRAL NERVOUS SYSTEM TUMOR CELL LINES

Abstract Background There is great interest in utilizing nanoparticles to improve drug delivery central nervous system (CNS) tumors, but the biologic features underlying successful at tumor site are not known. METHODS We developed a pooled screening assay investigate cellular predictive of nanoparticle and screened 35 fluorescent formulations against 488 cancer cell lines with DNA barcodes. The library was comprised nonlethal liposomal or polymeric cores varied surface functionality, including natural synthetic polymers. Cells were profiled using fluorescence-activated sorting barcodes sequenced deconvolved generate an association score for each nanoparticle-cell line pair. RESULTS Of lines, 22 lineages (tissues origin) included. derived from CNS tumors; these classified as astrocytoma glioblastoma, one oligodendroglioma, 2 medulloblastoma. 40% female patients average age derivation 52 years; TP53 hotspot mutations detected 25/35 PTEN 15/25 lines. Using unsupervised hierarchical clustering by profiles, did cluster together lineage, subtype, mutation status rather baseline expression genes involved nanocarrier trafficking. Nanoparticle profiles heterogeneous among most formulations, though had high polystyrene respect other lineages. Select uptake liposomes coated polymers fucoidan, alginate, hyaluronic acid chondroitin sulfate; trends further probed non-pooled screen 5 additional Conclusions Uptake across can be predicted gene expression.