Titanate Nanotube-Ionic Liquid Hybrid Biomaterials for Tunable Cytotoxicity and Radiosensitization in Cancer Cells

The development of biomaterials capable of modulating cellular response while integrating multiple therapeutic modalities remains a major challenge in cancer treatment. Herein, titanate nanotube (TNT)-ionic liquid (IL) hybrid biomaterials were engineered as tunable systems for combined chemotherapy and radiosensitization. Imidazolium- and pyridinium-based ILs with varying alkyl chain lengths were immobilized onto TNTs, generating hybrid materials with distinct physicochemical and biological profiles. Spectroscopic and chemometric analyses, together with TGA/DTG and electron microscopy, supported the successful formation of the TNT.IL hybrid biomaterials, revealing retained thermally detectable organic fractions and preservation of the nanotubular architecture in representative systems. Biological evaluation revealed a clear structure-function relationship, in which IL chain length governed cytotoxicity, while TNT functionalization modulated these effects, enabling both attenuation and enhancement of cellular responses. Long-chain ILs reduced cell viability to ∼10-25% at 20 μg·mL-1, whereas short-chain systems maintained >90% viability. In bladder cancer cells (T24), C10MImCl and TNT.C10MImCl exhibited dose- and time-dependent cytotoxicity. Notably, selected biocompatible hybrid systems enhanced radiosensitivity in glioblastoma models, reducing clonogenic survival in M059J cells from ∼73% to ∼42%. These findings demonstrate that TNT.IL hybrid biomaterials provide a versatile platform for engineering tunable biointerfaces with potential applications in cancer therapy.