Exploring Amino Acid-Capped Nanoparticles for Selective Anti-Parasitic Action and Improved Host Biocompatibility

Abstract

Toxoplasma gondii causes toxoplasmosis, a common infection against which better drugs are needed. Recently, we showed that inorganic nanoparticles have anti-Toxoplasma activity. Here, we sought to enhance the anti-parasitic efficacy and host biocompatibility of these nanoparticles by modifying their surface with amino acids. The amino acids used were selected based on the nutritional requirements of Toxoplasma gondii. Amino acid-capped nanoparticles (amino-NPs) were synthesized, purified, and then screened for anti-Toxoplasma activity in in vitro infection models. The amino-NPs showed enhanced anti-parasitic selectivity as well as improved host biocompatibility. Oxidative stress, modulation of host HIF-1α, and activation of the kynurenine pathway contributed to the anti-parasitic action of the amino-NPs. Our findings provide additional support for the potential use of nanoparticles as innovative anti-parasitic agents. Findings glean additional perspective that highlight prospects of nanoparticles not only as innovative source of anti-parasitic agents but also provide evidence for probable biological mechanism.

Nanoparticles show potential to retard bradyzoites in vitro formation of Toxoplasma gondii

“…Taken together, our data provide evidence for the anti-bradyzoite potential of NPs but demonstrate that the anti-T. gondii potential of NPs may not necessarily preclude bradyzoite formation. Our findings support the anti-parasitic action of NPs and are consistent with other reports that have demonstrated the anti-protozoal (Ahmad et al 2015, Rahul et al 2015, Saad et al 2015, Yah and Simate 2015, Saini et al 2016, including anti-T. gondii (Leyke et al 2012, Adeyemi et al 2017, 2018a, potential of NPs.…”

“…In the separate investigations, in vitro cellular toxicity by gold, silver or platinum nanoparticles have been reported at doses ≥ 100 µg/mL (Jiao et al 2014, Adeyemi et al 2018a. This dose is higher than the effective doses of nanoparticles used in the present study.…”

Cellular apoptosis of HFF cells by inorganic nanoparticles not susceptible to modulation by Toxoplasma gondii infection in vitro

“…The reason for this variance behavior in cellular apoptosis induction by NPs and amino-NPs is not known yet but may be attributed to change in surface chemistry of amino-NPs occasioned by conjugation of l-tryptophan. This line of thought is consistent with our earlier findings (Adeyemi et al, 2018b) in which NPs-tryptophan conjugates and NPs lacking this amino acid exhibited dissimilar cellular interactions. Furthermore, NPs and amino-NPs have demonstrated capacity to activate kynurenine pathway in vitro (Adeyemi et al, 2017b) by yet unknown mechanism.…”

“…Nanoparticles (NPs) with diameter size range of 5-40 nm, including silver (AgNP), gold (AuNP), platinum (PtNP) and amino-NPs (silvertryptophan -AgNP TRP and gold-tryptophan -AuNP TRP ) were gifted by Global Infection Unit, NRCPD, Obihiro University of Agriculture & Veterinary Medicine, Obihiro, Japan. Their synthesis and characterization have been reported elsewhere (Adeyemi et al, 2018b). The NPs were reconstituted in fresh culture medium prior to each use.…”

“…The biological assay was repeated three times, in triplicate. Selection of doses for the nanoparticles as well as for small molecules was premised on our earlier reports (Adeyemi et al, 2017a(Adeyemi et al, , 2017b(Adeyemi et al, , 2018b) and on preliminary experiments. In all the cases, doses were less than one third of the IC 50 value.…”