L-tryptophan-titanium oxide nanoparticles showed selective anti-Toxoplasma gondii activity and improved host biocompatibility - 29/04/23
Abstract |
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.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | Tryptophan-TiO2 nanoparticles (NPs) show selective anti-parasitic activity. |
• | The NPs induced ROS production and altered parasite redox status. |
• | These nanoparticles did not cause mitochondrial toxicity. |
Abbreviations : NPs, GSH, BSA, TiO2, Mo, EDS, FTIR, IC50, EC50
Keywords : Amino acids, Drug discovery, Medicinal biochemistry, Toxoplasmosis
Plan
Vol 162
Article 114597- juin 2023 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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