Salicylate-based biocompatible ionic liquids as selective modulators of antineoplastic agents cisplatin and doxorubicin

This study evaluated the cytotoxic effects of 30 ionic liquids ILs ) on non-transformed MRC-5 cells and their potential to enhance the efficacy of antineoplastic agents (cisplatin- cisPt , doxorubicin- DOXO , and paclitaxel- PTX ) on MRC-5 and HeLa cell lines. Initial screening using the MTT assay after 48-hour treatment identified twelve ILs ( IL1-6 , 12 , 16 , 18 , 19 , 20 , and 28 ) with less than 10% cytotoxicity in MRC-5 cells, which were further assessed via clonogenic assay; IL4 was excluded due to long-term cytotoxicity (> 0.9 survival fraction reduction). IC 50 values of cisPt , DOXO , and PTX were determined after 24- and 48-hour treatments, revealing higher sensitivity in HeLa cells compared to MRC-5. Combination treatments with selected salicylate-based IL12 and IL28 significantly reduced cytotoxicity on MRC-5 cells while increasing cytotoxicity on HeLa cells after 48 h, as confirmed by dose-response curves and selectivity indexes. PTX combinations showed no significant change in cytotoxicity. CisPt and DOXO displayed the most pronounced cytotoxicity against HeLa cells, with a corresponding enhancement in selectivity. The ionic liquids that demonstrated the greatest potential were those incorporating salicylate and cinnamate anions. These findings suggest that ILs can modulate the selectivity and efficacy of antineoplastic agents, potentially reducing required doses of well-known drugs in cancer therapy. Further studies are needed to elucidate ILs’ mechanisms and optimize their application as pharmaceutical co-solvents.