Mechanoregulation of titanium dioxide nanoparticles in cancer therapy

Titanium dioxide (TiO₂) nanoparticles (NPs), first developed in the 1990s, have been applied in numerous biomedical fields such as tissue engineering and therapeutic drug development. In recent years, TiO₂-based drug delivery systems have demonstrated the ability to decrease the risk of tumorigenesis and improve cancer therapy. There is increasing research on the origin and effects of pristine and doped TiO₂-based nanotherapeutic drugs. However, the detailed molecular mechanisms by which drug delivery to cancer cells alters sensing of gene mutations, protein degradation, and metabolite changes as well as its associated cumulative effects that determine the microenvironmental mechanosensitive metabolism have not yet been clearly elucidated. This review focuses on the microenvironmental influence of TiO₂-NPs induced various mechanical stimuli on tumor cells. The differential expression of genome, proteome, and metabolome after treatment with TiO₂-NPs is summarized and discussed. In the tumor microenvironment, mechanosensitive DNA mutations, gene delivery, protein degradation, inflammatory responses, and cell viability affected by the mechanical stimuli of TiO₂-NPs are also examined.