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 (TiO 2 ) and molybdenum (Mo) for their potential to inhibit the growth of T. gondii in vitro. NPs of TiO 2 and Mo showed non-dose-dependent anti- T. gondii activity with EC 50 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 TiO 2 , we modified the NP surface using alanine, aspartate, arginine, cysteine, glutamate, tryptophan, tyrosine, and bovine serum albumin. The bio-modified TiO 2 showed anti-parasite activity with EC 50 values ranging from 45.7 to 286.4 µg/mL. At effective anti-parasite concentrations, modified-TiO 2 showed no appreciable host cytotoxicity. Of the eight bio-modified TiO 2 , tryptophan-TiO 2 showed the most promising anti- T. gondii specificity and improved host biocompatibility with a selectivity index (SI) of 49.1 versus 7.5 for TiO 2 (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-TiO 2 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 TiO 2 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.
Il testo completo di questo articolo è disponibile in PDF.Graphical Abstract |
Highlights |
• | Tryptophan-TiO 2 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, TiO 2 , Mo, EDS, FTIR, IC 50 , EC 50
Keywords : Amino acids, Drug discovery, Medicinal biochemistry, Toxoplasmosis
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Vol 162
Articolo 114597- giugno 2023 Ritorno al numeroBenvenuto su EM|consulte, il riferimento dei professionisti della salute.
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