TY - JOUR
T1 - Gold nanoparticle-based conjugated nanotags as potential compounds against Trypanosoma brucei infection
AU - Rostán, Santiago
AU - Laing, Stacey
AU - Girard, Alexandre
AU - Scalese, Gonzalo
AU - Cooper, Anneli
AU - MacLeod, Annette
AU - Pérez-Díaz, Leticia
AU - Mahler, Graciela
AU - Faulds, Karen
AU - Graham, Duncan
AU - Otero, Lucía
PY - 2024/12/27
Y1 - 2024/12/27
N2 - 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.
AB - 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.
KW - gold nanoparticles
KW - metal-based drugs
KW - palladium complex
KW - trypanosomatid parasites
KW - SERS
UR - https://doi.org/10.17868/strath.00091667
U2 - 10.1021/acsanm.4c05201
DO - 10.1021/acsanm.4c05201
M3 - Article
SN - 2574-0970
VL - 7
SP - 28219
EP - 28228
JO - ACS Applied Nano Materials
JF - ACS Applied Nano Materials
IS - 24
ER -