Substituent Effects of Heptamethine Cyanine Dyes on Drug Uptake in Patient-Derived Glioma Cells.

Brain tumors, specifically high-grade gliomas such as glioblastoma (GBM), are challenging to treat due to the presence of physiological barriers such as blood-brain barrier (BBB) and tumor heterogeneity. Designing drugs that address these brain tumor-specific drug discovery challenges will herald much-needed breakthroughs for this patient population. This study presents a proof of concept for the in vitro cellular activity of the multitargeted kinase inhibitor crizotinib conjugated to BBB-crossing heptamethine cyanine dyes decorated with various functional groups in four patient-derived GBM cell lines. We also present evidence of cellular uptake, which contributes to the observed improvement in potency of the conjugates.