Yu Mengya, Zhu Lijuan, Dong Guoqi, Chen Jianjiao, Ruan Bankang, Liu Yi, Yi Shujuan, Meng Zhenqi, Chen Guanjian, Xu Weiping, Huang Jiaguo, Han Fanghai
State Key Laboratory of Anti-Infective Drug Discovery and Development, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Department of Gastrointestinal Surgery, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou 510317, China.
ACS Nano. 2024 Dec 31;18(52):35490-35506. doi: 10.1021/acsnano.4c12915. Epub 2024 Dec 16.
Sentinel lymph node biopsy holds significant importance in cancer management, yet the challenge persists in early detection and precise resection of metastasis lymph nodes (LNs) due to the absence of specific and sensitive optical probes. This study reports metastatic LN reporters (MLRs) with an activatable optical output for accurate spatiotemporal mapping of lymphatic metastases in gastric cancer. MLRs are self-assembled entities incorporating mixed amphiphiles with a lipophilic tail and a tumor-targeting ligand or a fluorescent moiety that is caged with a switch cleavable by tumor-specific β-galactosidase (β-Gal). After draining into LNs, MLRs selectively activate their near-infrared fluorescence in the presence of spreading tumor cells. In orthotopic gastric cancer mouse models, the representative reporter MLR1 distinguishes macro/micrometastatic LNs from benign LNs and enables early detection of skip LNs metastasis patterns in a spatial-dependent manner. Such an active sensing mechanism provides a high level of sensitivity and specificity comparable to those of flow cytometry analysis. In surgically resected patient specimens, MLR1 differentiates cancerous tissues and metastatic LNs from normal tissues and benign LNs within 1 h. This study thus presents NIRF nanoprobes that permit facile detection of LN metastases in GC patient samples and highlights a generic translatable nanoprobe design for understanding metastatic progression.
前哨淋巴结活检在癌症治疗中具有重要意义，但由于缺乏特异性和灵敏的光学探针，早期检测和精确切除转移淋巴结（LNs）仍然是一项挑战。本研究报告了具有可激活光学输出的转移淋巴结报告分子（MLRs），用于准确时空映射胃癌中的淋巴转移。MLRs是自组装实体，包含具有亲脂性尾部和肿瘤靶向配体或荧光部分的混合两亲分子，该荧光部分被肿瘤特异性β-半乳糖苷酶（β-Gal）可切割的开关所封闭。在引流到淋巴结后，MLRs在存在扩散的肿瘤细胞时选择性地激活其近红外荧光。在原位胃癌小鼠模型中，代表性报告分子MLR1可将宏观/微观转移淋巴结与良性淋巴结区分开来，并能够以空间依赖的方式早期检测跳跃式淋巴结转移模式。这种主动传感机制提供了与流式细胞术分析相当的高灵敏度和特异性。在手术切除的患者标本中，MLR1在1小时内就能将癌组织和转移淋巴结与正常组织和良性淋巴结区分开来。因此，本研究提出了近红外荧光纳米探针，可轻松检测GC患者样本中的淋巴结转移，并突出了一种通用的可转化纳米探针设计，用于理解转移进展。
