Metal-organic framework nanomaterials alter cellular metabolism in bladder cancer

Abstract

While nanomaterial-mediated metabolic reprogramming emerges as a promising anticancer strategy, the precise mechanisms remain elusive due to limited metabolomics investigations. The objective of this study is to design an aluminum (Al) based metal organic frameworks (Al-MOF) and investigate its cytotoxic effects on bladder cancer cells (T24), and elucidate the specific molecular mechanisms. Comprehensive characterization (scanning electron microscopy, particle size and potential analysis, infrared spectroscopy, powder X-ray diffraction, and N₂ desorption/desorption experiment) confirmed the successful preparation of Al-MOF. Subsequently, in vitro assays demonstrated the selective cytotoxicity of Al-MOF, showing an inhibitory effect on the proliferation of T24 compared to human immortalized urothelial cells. At the same time, when the concentration of Al-MOF exceeded 100 μg/mL, it exhibited significant migration inhibition on T24. Then, the effect of Al-MOF on T24 metabolites was investigated using ultra-high performance liquid chromatography quadrupole Orbitrap high-resolution mass spectrometry. After 24 h of incubation, we identified 38 key differential metabolites from expression patterns and metabolic pathways, predominantly in fatty acid synthesis. Research has found that Al-MOF reduced fatty acid biosynthesis by inhibiting FASN expression, thereby inhibiting the progression of T24. This work provides evidence of MOF-mediated intervention in cancer cell metabolism, offering valuable insights for the design of novel multifunctional nanotherapies.