Apoferritin and Apoferritin-Capped Metal Nanoparticles Inhibit Arginine Kinase of Trypanosoma brucei

Abstract

The aim of this study was to explore the inhibitory potential of apoferritin or apoferritin-capped metal nanoparticles (silver, gold and platinum) against Trypanosomabrucei arginine kinase. The arginine kinase activity was determined in the presence and absence of apoferritin or apoferritin-capped metal nanoparticles. In addition, kinetic parameters and relative inhibition of enzyme activity were estimated. Apoferritin or apoferritin-capped metal nanoparticles’ interaction with arginine kinase of T. brucei led to a >70% reduction in the enzyme activity. Further analysis to determine kinetic parameters suggests a mixed inhibition by apoferritin or apoferritin-nanoparticles, with a decrease in Vmax. Furthermore, the Km of the enzyme increased for both ATP and L-arginine substrates. Meantime, the inhibition constant (Ki) values for the apoferritin and apoferritin-nanoparticle interaction were in the submicromolar concentration ranging between 0.062 to 0.168 nM and 0.001 to 0.057 nM, respectively, for both substrates (i.e., L-arginine and ATP). Further kinetic analyses are warranted to aid the development of these nanoparticles as selective therapeutics. Also, more studies are required to elucidate the binding properties of these nanoparticles to arginine kinase of T. brucei.

Metallic Nanoparticles and Core-Shell Nanosystems in the Treatment, Diagnosis, and Prevention of Parasitic Diseases

“…Parasite adhesion is driven by particles present on the surface of the parasite or secreted during the infection process; these molecules bind to specific receptors on the host cells [ 110 ]. The human African trypanosomiasis is caused by the protozoan Trypanosoma brucei gambiense (milder form) and Trypanosoma brucei rhodesiense (associated with faster disease progression) that involve development of neuronal symptoms and higher mortality [ 30 , 111 ]. The disease occurs only in Sub-Saharan Africa and is transmitted by vectors—the flies of genus Glossina [ 112 , 113 , 114 ].…”

“…Gold nanoparticles were less effective against Trypanosoma congolense and Trypanosoma evansi , with an average ≤50% inhibition of parasite growth compared to silver nanoparticles, which were ≥70%. Gold and silver nanoparticles strongly and selectively inhibit recombinant Trypanosoma brucei arginine kinase [ 77 , 111 ]. Arginine kinase is a phosphotransferase that is essential for the growth and survival of Trypanosoma brucei, particularly in the bloodstream of the infected host because it helps the parasite meet required energy demands to maintain a reductive environment [ 24 , 77 ].…”

Rationally Designed Self-Assembling Nanovaccines Elicit Robust Mucosal and Systemic Immunity against Rhabdovirus

“…32 Like mammals and amphibians, IgM contributes predominantly to systemic immunity, which has been considered the principal Ig in plasma. 33 IgT (also called IgZ in zebrafish) is a specialized mucosal immunoglobulin, similar to IgA in mammals. 34 The biological function of IgD remains unclear.…”

“…Unlike mammals, only three Igs isotypes are identified in teleost, including IgM, IgT (IgZ in zebrafish), and IgD . Like mammals and amphibians, IgM contributes predominantly to systemic immunity, which has been considered the principal Ig in plasma . IgT (also called IgZ in zebrafish) is a specialized mucosal immunoglobulin, similar to IgA in mammals .…”