Metastatic status of sentinel lymph nodes in breast cancer determined with photoacoustic microscopy via dual-targeting nanoparticles

Abstract

Detection of sentinel lymph nodes (SLNs) is critical to guide the treatment of breast cancer. However, distinguishing metastatic SLNs from normal and inflamed lymph nodes (LNs) during surgical resection remains a challenge. Here, we report a CD44 and scavenger receptor class B1 dual-targeting hyaluronic acid nanoparticle (5K-HA-HPPS) loaded with the near-infra-red fluorescent dye DiR-BOA for SLN imaging in breast cancer. The small sized (~40 nm) self-assembled 5K-HA-HPPSs accumulated rapidly in the SLNs after intradermal injection. Compared with normal popliteal LNs (N-LN), there were ~3.2-fold and ~2.4-fold increases in fluorescence intensity in tumour metastatic SLNs (T-MLN) and inflamed LNs (Inf-LN), respectively, 6 h after nanoparticle inoculation. More importantly, photoacoustic microscopy (PAM) of 5K-HA-HPPS showed a significantly distinct distribution in T-MLN compared with N-LN and Inf-LN. Signals were mainly distributed at the centre of T-MLN but at the periphery of N-LN and Inf-LN. The ratio of PA intensity (R) at the centre of the LNs compared with that at the periphery was 5.93 ± 0.75 for T-MLNs of the 5K-HA-HPPS group, which was much higher than that for the Inf-LNs (R = 0.2 ± 0.07) and N-LNs (R = 0.45 ± 0.09). These results suggest that 5K-HA-HPPS injection combined with PAM provides a powerful tool for distinguishing metastatic SLNs from pLNs and inflamed LNs, thus guiding the removal of SLNs during breast cancer surgery.

Sentinel lymph node detection by combining nonradioactive techniques with contrast agents: State of the art and prospects

“…Regardless of the chemistry or physical structure of the contrast agent, the factor that controls lymphatic transport is the size (usually, the hydrodynamic diameter, associated with the particle size and surface potential) [228][229][230]. More specifically, the size of the contrast agent Forepaw injection [227] greatly affects uptake into the lymphatic system, speed of transport through the system and retention inside draining lymph nodes. As a consequence, the contrast agent size should be optimized toward specific intended applications such as intraoperative versus pre-/postoperative imaging, reduction of background noise and achievement of sufficient migration to highlight the SLNs and any lower tier nodes of interest [155].…”

Quantitative hypoxia mapping using a self-calibrated activatable nanoprobe

“…After purification, hydrophobic Cy7-1 was encapsulated in the internal cavities of PG5-Cy5 at a loading rate of 8% (Cy7-1/PG5-Cy5). The CD44 targeting group LWHA [ 21 ] was coated on the surface of Cy7-1/PG5-Cy5 to form Cy7-1/PG5-Cy5@LWHA. After purification, Cy7-1/PG5-Cy5@LWHA was characterized using Fourier transform infrared spectroscopy (Figure S1).…”

Targeted contrast agents and activatable probes for photoacoustic imaging of cancer

“…Due to its high specificity and binding affinity towards CD44, it can be exploited as a ligand in the design of CD44-targeted molecules including TCAs for PA imaging. 13–15,62,65–68…”

“…4c). 68 A critical design element of this TCA includes HA ligands which can target CD44 and the intrinsic ability of HPPS to interact with scavenger receptor class B type 1, both of which are expressed on the surface of certain breast cancer cells. To provide contrast, a NIR cyanine dye (DiR-BOA) was encapsulated within 5K-HA-HPPS since it can generate a robust PA signal upon irradiation.…”