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Chain-like gold nanoparticle clusters for multimodal photoacoustic microscopy and optical coherence tomography enhanced molecular imaging.

ABSTRACT: Colloidal gold nanoparticles (GNPs) serve as promising contrast agents in photoacoustic (PA) imaging, yet their utility is limited due to their absorption peak in the visible window overlapping with that of hemoglobin. To overcome such limitation, this report describes an ultrapure chain-like gold nanoparticle (CGNP) clusters with a redshift peak wavelength at 650 nm. The synthesized CGNP show an excellent biocompatibility and photostability. These nanoparticles are conjugated with arginine-glycine-aspartic acid (RGD) peptides (CGNP clusters-RGD) and validated in 12 living rabbits to perform multimodal photoacoustic microscopy (PAM) and optical coherence tomography (OCT) for visualization of newly developed blood vessels in the sub-retinal pigment epithelium (RPE) space of the retina, named choroidal neovascularization (CNV). The PAM system can achieve a 3D PAM image via a raster scan of 256 × 256 pixels within a time duration of 65 s. Intravenous injection of CGNP clusters-RGD bound to CNV and resulted in up to a 17-fold increase in PAM signal and 176% increase in OCT signal. Histology indicates that CGNP clusters could disassemble, which may facilitate its clearance from the body.

SUBMITTER: Nguyen VP

PROVIDER: S-EPMC7782787 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Usher syndrome type 2A (USH2A) is a genetic disorder characterized by retinal degeneration and hearing loss. To better understand the pathogenesis and progression of this syndrome, animal models such as USH2A knockout (USH2AKO) rabbits have been developed. In this study, we employed multimodal imaging techniques, including photoacoustic microscopy (PAM), optical coherence tomography (OCT), fundus autofluorescence (FAF), fluorescein angiography (FA), and indocyanine green angiography (ICGA) imaging to evaluate the retinal changes in the USH2AKO rabbit model. Twelve New Zealand White rabbits including USH2AKO and wild type (WT) were used for the experiments. Multimodal imaging was implemented at different time points over a period of 12 months to visualize the progression of retinal changes in USH2AKO rabbits. The results demonstrate that ellipsoid zone (EZ) disruption and degeneration, key features of Usher syndrome, began at the age of 4 months old and persisted up to 12 months. The EZ degeneration areas were clearly observed on the FAF and OCT images. The FAF images revealed retinal pigment epithelium (RPE) degeneration, confirming the presence of the disease phenotype in the USH2AKO rabbits. In addition, PAM images provided high-resolution and high image contrast of the optic nerve and the retinal microvasculature, including retinal vessels, choroidal vessels, and capillaries in three-dimensions. The quantification of EZ fluorescent intensity using FAF and EZ thickness using OCT provided comprehensive quantitative data on the progression of degenerative changes over time. This multimodal imaging approach allowed for a comprehensive and non-invasive assessment of retinal structure, microvasculature, and degenerative changes in the USH2AKO rabbit model. The combination of PAM, OCT, and fluorescent imaging facilitated longitudinal monitoring of disease progression and provided valuable insights into the pathophysiology of USH2A syndrome. These findings contribute to the understanding of USH2A syndrome and may have implications for the development of diagnostic and therapeutic strategies for affected individuals. The multimodal imaging techniques employed in this study offer a promising platform for preclinical evaluation of potential treatments and may pave the way for future clinical applications in patients with Usher syndrome.

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Chain-like gold nanoparticle clusters for multimodal photoacoustic microscopy and optical coherence tomography enhanced molecular imaging.

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