IN VIVO BIODISTRIBUTION AND TOXICITY ASSESSMENT OF PEGYLATED GOLD AND SILVER NANOPARTICLES: INDIVIDUAL VERSUS CO-ADMINISTRATION VIA INTRAVENOUS ROUTE

Abstract

Gold (AuNPs) and silver (AgNPs) nanoparticles (NPs) have drawn significant attention in biomedical research due to their distinctive physicochemical properties, which govern their biological interactions. A comprehensive understanding of the nano-bio interface is essential for advancing therapeutic applications with favorable pharmacokinetic and pharmacodynamic profiles in drug delivery, imaging, and diagnostics. Multiplexed simultaneous analysis using co-administered metallic nanoparticles offers a promising strategy to assess critical parameters-such as size, shape, and surface chemistry-that influence the nano-bio interface. However, evaluating toxicity is imperative, as biocompatibility is a prerequisite for the safe and effective use of these NPs as biomedical probes. This study explores the biodistribution, potential toxicity, and metabolic alterations associated with the intravenous administration of AuNPs and AgNPs-either individually or combined-in a rat model. Spherical polyethylene glycol (PEG)-modified AuNPs and AgNPs with particle sizes of 13 nm and 20 nm, respectively, were synthesized and administered to 24 rats, equally divided into four groups: control, PEG-AuNPs, PEG-AgNPs, and a coadministration group receiving both PEG-AuNPs and PEG-AgNPs. Serum and organ tissues were collected 24 hours post-injection. Biodistribution was analyzed using inductively coupled plasma-mass spectrometry (ICP-MS), toxicity was assessed via real-time polymerase chain reaction (RT-PCR), and metabolic changes were evaluated using liquid chromatographytandem mass spectrometry (LC-MS/MS) and flow injection analysis-tandem mass spectrometry (FIA-MS/MS). The results demonstrated significant accumulation of PEG-AuNPs and PEG-AgNPs in the blood, liver, and spleen, with no detectable toxicity. Metabolic profiling revealed that PEG AuNPs notably affected sphingomyelin levels, bile acid metabolism, and cholesterol esters, indicating potential disruptions in lipid homeostasis and pyrimidine/purine metabolism. Importantly, the co-administration of PEG-AuNPs and PEG-AgNPs did not significantly alter biodistribution patterns or induce additional toxicity compared to individual administration. These findings provide critical insights into the biological interactions of PEGylated AuNPs and AgNPs, underscoring the significance of administration strategies in nanomedicine.