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

• Published in: Light, science & applications Vol. 9; no. 1; p. 164
• Main Authors: Dai, Yanfeng, Yu, Xiang, Wei, Jianshuang, Zeng, Fanxin, Li, Yiran, Yang, Xiaoquan, Luo, Qingming, Zhang, Zhihong
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16.09.2020; Springer Nature B.V
• Subjects: 639/624/1107; 639/624/399; Applied and Technical Physics; Atomic; Breast cancer; Cancer surgery; CD44 antigen; Classical and Continuum Physics; Dyes; Fluorescent indicators; Hyaluronic acid; Inflammation; Injection; Inoculation; Lasers; Lymph nodes; Lymphatic system; Mastectomy; Metastases; Metastasis; Microscopy; Molecular; Nanoparticles; Optical and Plasma Physics; Optical Devices; Optics; Photonics; Physics; Physics and Astronomy; Researchers; Scavenger receptors; Surgery; Tumors
• ISSN: 2047-7538; 2095-5545; 2047-7538
• DOI: 10.1038/s41377-020-00399-0

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. Breast cancer: nanoparticles highlight problematic lymph nodes Fluorescent nanoparticles designed by researchers in China will help surgeons detect key sites where breast cancer spreads around the body. Tumours undergoing metastasis start by targeting sentinel lymph nodes, which are difficult to distinguish from normal or inflamed lymph nodes. Zhihong Zhang at Huazhong University of Science and Technology, Wuhan and co-workers, designed nanoparticles just 40 nm in size coated in hyaluronic acid, which binds to proteins overexpressed by breast cancer cells. The nanoparticles also include fluorescent dye molecules that are easily detected by photoacoustic microscopy. Six hours after injecting the nanoparticles into mice, the researchers observed strong photoacoustic signals at the centres of sentinel lymph nodes, while other lymph nodes showed signals only at their edges. This ability to distinguish important metastatic sites will guide surgeons in removing problematic tissue during breast cancer surgery.