L-tryptophan-titanium oxide nanoparticles showed selective anti-Toxoplasma gondii activity and improved host...

Toxoplasma gondii, the etiological agent of toxoplasmosis, currently affects nearly one-third of the human population. Treatment options for toxoplasmosis are limited, which underscores the need for new drugs. In the present study, we screened nanoparticles (NPs) of titanium dioxide (TiO₂) and molybdenum (Mo) for their potential to inhibit the growth of T. gondii in vitro. NPs of TiO₂ and Mo showed non-dose-dependent anti-T. gondii activity with EC₅₀ values of 157.6 and 253 µg/mL, respectively. Previously, we showed that amino acid modification of NPs enhances their selective anti-parasite toxicity. Therefore, to enhance the selective anti-parasitic action of TiO₂, we modified the NP surface using alanine, aspartate, arginine, cysteine, glutamate, tryptophan, tyrosine, and bovine serum albumin. The bio-modified TiO₂ showed anti-parasite activity with EC₅₀ values ranging from 45.7 to 286.4 µg/mL. At effective anti-parasite concentrations, modified-TiO₂ showed no appreciable host cytotoxicity. Of the eight bio-modified TiO₂, tryptophan-TiO₂ showed the most promising anti-T. gondii specificity and improved host biocompatibility with a selectivity index (SI) of 49.1 versus 7.5 for TiO₂ (note, pyrimethamine, a standard drug for toxoplasmosis, has an SI of 2.3). Furthermore, our data indicate that redox modulation may be part of the anti-parasite action of these NPs. Indeed, augmentation with trolox and l-tryptophan reversed the growth restriction caused by the tryptophan-TiO₂ NPs. Collectively, these findings suggest that the parasite toxicity was selective and not a result of general cytotoxic action. Furthermore, surface modification with amino acids such as l-tryptophan not only enhanced the anti-parasitic action of TiO₂ but also improved the host biocompatibility. Overall, our findings indicate that the nutritional requirements of T. gondii represent a viable target for the development of new and effective anti-T. gondii agents.