Tri-metallic (Au–Pt–Ag) nanofluids: unveiling synergistic anti-malarial, cytotoxic, and antioxidant potentials through experimental and computational approaches

Abstract

This study investigates the potent antimalarial, antioxidant, and cytotoxic properties of trimetallic (Au–Pt–Ag) nanofluids, integrating experimental validation with computational insights from advanced density functional theory (DFT) calculations. The antimalarial assays demonstrated that Au–Pt–Ag nanofluids exhibit a remarkable IC₅₀ value of 0.46 ± 0.004 μg mL⁻¹, indicating significant efficacy, particularly in comparison to standard drugs like chloroquine (IC₅₀ = 0.25 ± 0.006 μg mL⁻¹). Antioxidant activity, assessed via the DPPH assay, showed a dose-dependent increase in radical scavenging, with an IC₅₀ of 4.54 ± 0.26 μM. In vitro cytotoxicity studies on the human HepG2 cell line confirmed the nanofluids' biocompatibility, with significantly lower toxicity (IC₅₀ = 65.56 ± 1.57 μg mL⁻¹) than chloroquine (IC₅₀ = 388 ± 12.34 μM). Computational studies further reinforced these findings, as DFT calculations provided insights into the nanofluids' electronic structure and reactivity, while molecular docking and molecular dynamics simulations revealed strong and stable interactions with Plasmodium falciparum proteins. The high degree of correlation between experimental and computational results confirms the reliability of these nanofluids in targeting malaria. Additionally, ADMET profiling highlighted their optimal pharmacokinetic properties, including efficient intestinal absorption, minimal CNS penetration, and favorable metabolic characteristics. The coherence between computational predictions and experimental observations underscores the robustness of Au–Pt–Ag nanofluids as next-generation therapeutic agents for malaria and oxidative stress-related disorders, paving the way for further preclinical investigations and clinical applications.