Ligand Tethered Gold Nanoparticles against Untamed and Drug Resistant Leishmania Donovani

Introduction: Gold nanoparticles (Aunp) are useful tools in chemical biology interfaces. Engineered Aunps in sub-100 nm ranges are often successful in cancer chemotherapy and infections control. We have designed... [ view full abstract ]

Introduction: Gold nanoparticles (Aunp) are useful tools in chemical biology interfaces. Engineered Aunps in sub-100 nm ranges are often successful in cancer chemotherapy and infections control. We have designed quasi-spherical Aunps and functionalized them further in lactoferrin conjugation reactions. New generation ligand tethered nanoparticles were experimented successfully against Leishmania donovani parasites.
Methods: Green synthesis for highly mono-dispersed Aunps was carried out using gallic acid. Reductive formation of Aunps at 40C under sonication was monitored in Uv-Vis spectrophotometer and the particles recovered by centrifugation 16000 rpm, 30 min. Aunps were re-suspended in water and conjugated in 1,2 ethylenediamine. Human lactoferrin (Lf) was further functionalized onto Aunps in EDC-NHS reactions. Plasmonic Lf-Aunps uptake in mouse peritoneal macrophage was monitored and leishmanicidal efficacy against axenic and macrophage infested L. donovini AG 83 strains were studied in depth.
Results and Discussion: Aunps formation was monitored in Uv-Vis spectrophotometer (Fig 1). Aunps appeared quasi-spherical with average TEM size near 7.6 nm. The zeta potential was recorded at – 24.2 mv and PDI was 0.21. Lf-Aunps observed relative increase in size (Fig 1E) and the zeta potential was -18.2 mv. Diffractions indexed in XRD studies were at (1 1 1), (2 0 0), (2 2 0) and (3 1 1). Aunp and Lf-Aunp mass compositions were analyzed in ICP-EES. Lf-Aunps were exceedingly effective against both axenic and the macrophage resident amastigotes. Comparative evaluations under culture conditions confirmed Lf-Aunp IC50 4.1±1 μM and 2.0±0.3 μM against L. donovini AG83 axenic and macrophage infested forms. Lf-Aunps were equally effective against sodium stibogluconate resistant strains but were refractory in paromomycin resistant organisms. Nanoparticle remarkable efficacy against macrophage infested leishmania was reasoned due to targeted transport, rapid uptake and ani-oxidant potentials.


Figure 1: Nanoparticles synthesis and efficacy against L. donovini AG83.
Nanoparticle(Aunp) TEM,A; SAED,B; Plasmonic response in time scale, C; In different gallic acid concentrations, D; Lf-Aunp TEM studies,E; Lf-Aunp TEM uptake in macrophages
(30 min exposure),F.