Renally Clearable Ultraminiature Chain-Like Gold Nanoparticle Clusters for Multimodal Molecular Imaging of Choroidal Neovascularization

Abstract

Currently, available gold nanoparticles (GNPs) typically accumulate in the liver and spleen, leading to concerns for their long-term biosafety. To address this long-standing problem, ultraminiature chain-like gold nanoparticle clusters (GNCs) are developed. Via self-assembly of 7–8 nm GNP monomers, GNCs provide redshifted optical absorption and scattering contrast in the near-infrared window. After disassembly, GNCs turn back to GNPs with a size smaller than the renal glomerular filtration size cutoff, allowing their excretion via urine. A one-month longitudinal study in a rabbit eye model demonstrates that GNCs facilitate multimodal molecular imaging of choroidal neovascularization (CNV) in vivo, non-invasively, with excellent sensitivity and spatial resolution. GNCs targeting αvβ3 integrins enhance photoacoustic and optical coherence tomography (OCT) signals from CNV by 25.3-fold and 150%, respectively. With excellent biosafety and biocompatibility demonstrated, GNCs render a first-of-its-kind nanoplatform for biomedical imaging.A first-of-its-kind multifunctional ultraminiature chain-like gold nanoparticle clusters (GNCs) are developed via self-assembly of 7–8 nm spherical GNP monomers, the GNCs provides redshifted optical absorption and scattering contrasts in the near-infrared (NIR) window which is highly desired by optical imaging modalities such as photoacoustic (PA) imaging and optical coherence tomography (OCT). After disassembly, the GNCs turn back into ultraminiature GNPs with a size smaller than the renal glomerular filtration size cutoff, allowing them to be excreted via urine instead of being trapped in the liver and spleen. Renally clearable ultraminiature GNCs facilitate long-term multimodal molecular imaging of choroidal neovascularization in vivo.