Targeted gadolinium-labeled gold nanoparticles for MR imaging of C-reactive protein

Abstract

C-reactive protein (CRP) is rapidly upregulated during the early stages of inflammation following injury, infection, or illness and binds to damaged cells in affected tissues, making it an attractive target for imaging. Current clinical assays measure only circulating CRP levels and provide no spatial information about the location of inflammation or its structural impact. Direct visualization of CRP in tissues could enable earlier detection, precise localization of pathology, monitoring of treatment response, and identification of subclinical disease. Here, we report the development of the first CRP-targeted magnetic resonance (MR) imaging contrast agent for molecular imaging of inflammation. We synthesized a gadolinium-labeled gold nanoparticle (AuNP) targeted to CRP through a phosphocholine (PC) ligand, termed PC-Gd@AuNP. The resulting particles were highly uniform (∼2 nm) with a tunable Gd:PC surface ratio. Biophysical characterization demonstrated strong binding affinity for CRP (K_D = 135 ± 63.96 nM) and specificity in a complex biological fluid model. PC-Gd@AuNPs displayed high longitudinal relaxivity (8.5 mM⁻¹ s⁻¹ per Gd) and cytotoxicity thresholds (LC₅₀) of 1 μM in HeLa cells and 0.284 μM in HepG2 cells. These findings establish PC-Gd@AuNPs as a promising molecular MRI contrast agent with the potential to directly image CRP deposition in inflamed tissues and advance noninvasive detection and monitoring of inflammatory diseases.