靶向DLL3多功能纳米球高效精准检测小细胞肺癌循环肿瘤细胞的研究

Small cell lung cancer (SCLC) seriously threatens human health. Precision medicine which relays on efficient and accurate diagnosis to cancer is key to improve the prognosis of SCLC. Efficient and accurate detection of circulating tumor cells (CTCs) is a technical challenge for precision medical treatment in SCLC. But traditional CTC immune magnetic separation technology with the immune capture target of epithelial cell adhesion molecule (EpCAM) lacks tumor specificity and tissue type specificity, and no specific CTC detection method has been developed in SCLC. Screening SCLC specific immune capture target is the key to solve this problem. Our previous study found that the expression of Delta-like ligand 3 (DLL3) is specific and plenteous in SCLC, and DLL3 may be a potential target for SCLC-specific CTC immunocapture. The aim of this project is to construct a multifunctional nanospheres targeting DLL3, and to investigate the feasibility and specific methods of targeting DLL3 multifunctional nanospheres to detect CTC in SCLC cell lines and clinical blood samples. And we are looking forward to providing a new method and target for accurate diagnosis of SCLC.

小细胞肺癌（SCLC）恶性程度高，个体化精准医疗是改善SCLC预后的方向。高效精准的循环肿瘤细胞（CTC）检测技术是SCLC精准医疗的技术难题。目前广泛应用的以上皮细胞粘附分子（EpCAM）为免疫识别靶点的CTC检测存在明显缺陷，尚缺乏SCLC特异性CTC检测方法，寻找SCLC特异性免疫识别靶点是解决这一问题的关键。我们发现Delta样配体3（DLL3）在SCLC中特异性、高水平膜表达，提示DLL3可能是极具潜力的SCLC特异性CTC免疫识别靶点。本课题拟构建靶向DLL3多功能纳米球，在SCLC细胞系及患者血标本中，探索靶向DLL3多功能纳米球高效精准捕获小细胞肺癌CTC的可行性及具体方法，为SCLC精准医疗提供技术支持。

本项目围绕创立新型小细胞肺癌 CTC 分选技术开展相关研究工作，拟建立靶向 DLL3 的荧光-磁性-生物靶向多功能纳米球检测系统，拟以 SCLC 细胞系和SCLC 患者血标本为基础，探讨靶向 DLL3 的荧光-磁性-生物靶向多功能纳米球高效精准检测小细胞肺癌 CTC 的可行性及具体方法。我们实验组自主构建了靶向 DLL3 的荧光-磁性-生物靶向多功能纳米球，在单一环境下能够捕获SCLC细胞系，单一环境中，最佳磁珠浓度是0.3mg/ml，最佳孵育时间是20分钟。在小细胞肺癌细胞系（DMS114、NCI-H209、DMS153）中DLL3多功能纳米球比EpCAM多功能纳米球捕获率更高。在非小细胞肺癌（H157，H226）和人外周血白血病细胞（Jurkat T）中，DLL3多功能纳米球的捕获率均较低，提示DLL3多功能纳米球比EpCAM多功能纳米球对小细胞肺癌CTC捕获率更高，并且后续结果显示捕获SCLC特异性也更强。在病人血中也进行了探索，结果显示DLL3多功能纳米球比EpCAM多功能纳米捕获CTC能力相似。.