Gold Nanoparticle-Based\nConjugated Nanotags as Potential\nCompounds against Trypanosoma brucei Infection

In the search for alternatives for the treatment of parasitic\nneglected\ntropical diseases (NTD), an approach combining metal-based drug design\nand nanotechnology has been developed. On one hand, a potential metal-based\ndrug of the formula [PdCl(L1)], where L1 is a coumarin-thiosemicarbazone\nhybrid ligand, had been previously reported. This compound demonstrated\nactivity <i>in vitro</i> and <i>in vivo</i> against Trypanosoma cruzi, the etiological agent of Chagas\ndisease. On the other hand, conjugation of gold nanoparticles (AuNPs)\nto biologically active compounds has shown to enhance drug delivery\nand efficacy. In this work, these approaches were combined to successfully\nconjugate [PdCl(L1)] with AuNPs containing a Raman reporter for intracellular\ntracking. The aim of this conjugation was to exploit the potential\nof the nanoparticles as carriers and the metal complex as an antiparasitic\nagent. Conjugated nanotags were fully characterized and both the free\npalladium complex and the conjugates were tested against Trypanosoma brucei brucei (T. b. b.), the causative agent of a related NTD, African Trypanosomiasis.\nThe results showed that the conjugated nanotags [Pd(L1)-AuNPs] (IC<sub>50</sub> = 3.22 μM) demonstrated almost a 5-fold increase in\nthe anti-T. b. b. activity in comparison\nwith [PdCl(L1)] alone (IC<sub>50</sub> = 15.32 μM) and twice\nthe activity of the unconjugated nanoparticles (IC<sub>50</sub> =\n6.14 μM). In addition, the preliminary imaging using Raman microscopy\nand surface-enhanced Raman scattering (SERS) experiments revealed\nthe successful uptake of [Pd(L1)-AuNPs] by parasites. Although the <i>in vitro</i> selectivity was not improved postconjugation, the\npromising antitrypanosomatid activity of these conjugates warrant\nevaluation for performance and selectivity through future <i>in vivo</i> studies. This research paves the way for further\nexploration of the developed strategy in the fight against parasitic\ninfections.