Gold nanoparticle-based conjugated nanotags as potential compounds against Trypanosoma brucei infection

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Rostán, Santiago and Laing, Stacey and Girard, Alexandre and Scalese, Gonzalo and Cooper, Anneli and MacLeod, Annette and Pérez-Díaz, Leticia and Mahler, Graciela and Faulds, Karen and Graham, Duncan and Otero, Lucía (2024) Gold nanoparticle-based conjugated nanotags as potential compounds against Trypanosoma brucei infection. ACS Applied Nano Materials, 7 (24). pp. 28219-28228. ISSN 2574-0970 (https://doi.org/10.1021/acsanm.4c05201)

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Abstract

In the search for alternatives for the treatment of parasitic neglected tropical diseases (NTD), an approach combining metal-based drug design and nanotechnology has been developed. On one hand, a potential metal-based drug of the formula [PdCl(L1)], where L1 is a coumarin-thiosemicarbazone hybrid ligand, had been previously reported. This compound demonstrated activity in vitro and in vivo against Trypanosoma cruzi, the etiological agent of Chagas disease. On the other hand, conjugation of gold nanoparticles (AuNPs) to biologically active compounds has shown to enhance drug delivery and efficacy. In this work, these approaches were combined to successfully conjugate [PdCl(L1)] with AuNPs containing a Raman reporter for intracellular tracking. The aim of this conjugation was to exploit the potential of the nanoparticles as carriers and the metal complex as an antiparasitic agent. Conjugated nanotags were fully characterized and both the free palladium complex and the conjugates were tested against Trypanosoma brucei brucei (T. b. b.), the causative agent of a related NTD, African Trypanosomiasis. The results showed that the conjugated nanotags [Pd(L1)-AuNPs] (IC50 = 3.22 μM) demonstrated almost a 5-fold increase in the anti-T. b. b. activity in comparison with [PdCl(L1)] alone (IC50 = 15.32 μM) and twice the activity of the unconjugated nanoparticles (IC50 = 6.14 μM). In addition, the preliminary imaging using Raman microscopy and surface-enhanced Raman scattering (SERS) experiments revealed the successful uptake of [Pd(L1)-AuNPs] by parasites. Although the in vitro selectivity was not improved postconjugation, the promising antitrypanosomatid activity of these conjugates warrant evaluation for performance and selectivity through future in vivo studies. This research paves the way for further exploration of the developed strategy in the fight against parasitic infections.

ORCID iDs

Rostán, Santiago, Laing, Stacey ORCID logoORCID: https://orcid.org/0000-0001-5781-349X, Girard, Alexandre ORCID logoORCID: https://orcid.org/0000-0002-4334-5303, Scalese, Gonzalo, Cooper, Anneli, MacLeod, Annette, Pérez-Díaz, Leticia, Mahler, Graciela, Faulds, Karen ORCID logoORCID: https://orcid.org/0000-0002-5567-7399, Graham, Duncan ORCID logoORCID: https://orcid.org/0000-0002-6079-2105 and Otero, Lucía;
CORE (COnnecting REpositories)