State Key Laboratory of Systems Medicine for Cancer, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, PR China; Hunan Institute of Advanced Sensing and Information Technology, Xiangtan University, Xiangtan 411105, PR China.
Department of Breast Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, PR China.
Biomaterials. 2024 Jul;308:122538. doi: 10.1016/j.biomaterials.2024.122538. Epub 2024 Mar 27.
Surface-enhanced Raman spectroscopy (SERS) nanotags have garnered much attention as promising bioimaging contrast agent with ultrahigh sensitivity, but their clinical translation faces challenges including biological and laser safety. As breast sentinel lymph node (SLN) imaging agents, SERS nanotags used by local injection and only accumulation in SLNs, which were removed during surgery, greatly reduce biological safety concerns. But their clinical translation lacks pilot demonstration on large animals close to humans. The laser safety requires irradiance below the maximum permissible exposure threshold, which is currently not achievable in most SERS applications. Here we report the invention of the core-shell SERS nanotags with ultrahigh brightness (1 pM limit of detection) at the second near-infrared (NIR-II) window for SLN identification on pre-clinical animal models including rabbits and non-human primate. We for the first time realize the intraoperative SERS-guided SLN navigation under a clinically safe laser (1.73 J/cm) and identify multiple axillary SLNs on a non-human primate. No evidence of biosafety issues was observed in systematic examinations of these nanotags. Our study unveils the potential of NIR-II SERS nanotags as appropriate SLN tracers, making significant advances toward the accurate positioning of lesions using the SERS-based tracer technique.
表面增强拉曼光谱（SERS）纳米标签作为超灵敏的有前途的生物成像对比剂受到了广泛关注，但它们的临床转化面临着包括生物和激光安全性在内的挑战。作为乳腺前哨淋巴结（SLN）成像剂，通过局部注射使用的 SERS 纳米标签仅在 SLN 中积累，而 SLN 在手术中被切除，这大大降低了生物安全性问题。但它们的临床转化缺乏接近人类的大动物的试点示范。激光安全性要求辐照度低于最大允许暴露阈值，而目前大多数 SERS 应用都无法达到这一要求。在这里，我们报告了具有超高亮度（1 pM 检测限）的核壳 SERS 纳米标签的发明，该标签可在包括兔子和非人类灵长类动物在内的临床前动物模型中用于 SLN 识别。我们首次在临床安全激光（1.73 J/cm）下实现了术中 SERS 引导的 SLN 导航，并在非人类灵长类动物上识别出多个腋窝 SLN。在对这些纳米标签进行的系统检查中，没有观察到生物安全问题的证据。我们的研究揭示了近红外二区 SERS 纳米标签作为适当的 SLN 示踪剂的潜力，为使用基于 SERS 的示踪剂技术准确定位病变提供了重要进展。
