Laser-Ablated Gold Nanoparticles as Tunable Contrast Agents for Preclinical Imaging

Femtosecond laser-ablated gold nanoparticles (AuNPs) offer a unique platform for developing novel cost-effective contrast agents due to their ultraclean, surfactant-free synthesis and precisely tunable surface properties. This study developed three computed tomography (CT) contrast agents from a single stock solution of laser-ablated AuNPs, functionalized with polyethylene glycol (PEG-2kDa, PEG-4kDa), or lipoic acid with bovine serum albumin (BSA). The primary objective was to evaluate the safety and functional efficacy of these coated AuNPs in healthy and tumor-bearing mice. After a single intravenous injection (690 ± 30 mg Au/kg), all formulations were well tolerated with no acute toxicity observed. PEGylated AuNPs demonstrated long blood half-life (18 ± 2 h for PEG-2kDa; 37 ± 2 h for PEG-4kDa), making them suitable for cardiovascular imaging up to 24 h post-injection. BSA-AuNPs had a rapid blood clearance (T_1/2 = 2.8 ± 0.9 h), permitting cardiovascular assessment during the first 3 h, and provided intense, persistent contrast in abdominal organs, enabling liver imaging from 5 min and spleen imaging from 1 h post-injection. In a Ca755 mammary adenocarcinoma model, PEGylated AuNPs selectively accumulated in the tumor stroma and fibrous septa, allowing for precise tumor margin delineation and analysis of internal architecture. The findings establish that a single AuNP stock can be used to produce specialized contrast agents for specific imaging applications.