Silica-coated gold nanoplates as stable photoacoustic contrast agents for sentinel lymph node imaging

Abstract

A biopsy of the first lymph node to which a tumor drains – the sentinel lymph node (SLN) – is commonly performed to identify micrometastases. Image guidance of the SLN biopsy procedure has the potential to improve its accuracy and decrease its morbidity. We have developed a new stable contrast agent for photoacoustic image-guided SLN biopsy: silica-coated gold nanoplates (Si-AuNPs). The Si-AuNPs exhibit high photothermal stability when exposed to pulsed and continuous wave laser irradiation. This makes them well-suited for in vivo photoacoustic imaging. Furthermore, Si-AuNPs are shown to have low cytotoxicity. We tested the Si-AuNPs for SLN mapping in a mouse model where they exhibited a strong, sustained photoacoustic signal. Real-time ultrasound and photoacoustic imaging revealed that the Si-AuNPs quickly drain to the SLN gradually spreading throughout a large portion of the node.

Sentinel Lymph Node Biopsy Revisited: Ultrasound-Guided Photoacoustic Detection of Micrometastases Using Molecularly Targeted Plasmonic Nanosensors

“…This indicates that the optimal time point to perform imaging occurs in the first few hours after the injection. Furthermore, the two hour timescale is consistent with nanoparticle drainage through the lymphatics observed in vivo (32, 33) and cellular uptake of MAPS observed in vitro (34). Taken together, these observations provide additional support to the conclusion that the highly localized signal is due to tumor-cell mediated activation of MAPS.…”

Label-free Detection of Lymph Node Metastases with US-guided Functional Photoacoustic Imaging

“…It combines the high resolution of US with excellent optical contrast. By administering optically absorbing contrast agents, SLN mapping has been demonstrated in small-animal models (20)(21)(22)(23). Furthermore, by targeting plasmonic nanoparticles to cell surface receptors associated with the primary tumor, sensitive detection of micrometastases can be achieved (24).…”

The Effect of Laser Power on Photothermoacoustic Imaging of Blood Containing Gold Nanoparticles and Deoxygenation using a Frequency-Domain Phased Array Probe: An In-vitro Assay

“…The medical imaging modality employed for detection of malignant tumors in organs such as breast cancer should provide high-specificity to cancer and high resolution for early In situ detection [18]. Since, the main strength of PAI is its ability to obtain functional, anatomical and molecular information in real-time with a high resolution at clinically relevant depths, therefore either endogenous biomolecules such as hemoglobin, melanin and carotonoids or exogenous contrast agents such as indocyanine green [19], nanoparticles [20,21], nanoshells [22,23], nanorods [24,25], nanocages [26,27], and nanodiamonds [28] can be employed for image enhancement. However, as it will be discussed, for in vivo applications the nanostructures must be active targeted by conjugating them with suitable moieties e.g., antibodies, peptides or folates to prevent from protein adsorption and aggregation.…”