School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
Guangdong Province Engineering Technology Centre for Molecular Probe and Bio-Medical Imaging, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
J Exp Clin Cancer Res. 2022 Jun 13;41(1):201. doi: 10.1186/s13046-022-02393-3.
Breast cancer targeting diagnostic agent with effective imaging ability is important in guiding plan formulation, prediction, and curative effect evaluation of tumors in clinic. A tumor-targeting nanoprobe based on the functional and programmable Liquid-Liquid phase separation of AS1411 promoted by Ru(II) complex RuPEP may develop into a potential phosphorescence probe to detect breast cancer cells, where AS1411 act as a tumor-targeting guidance moiety to distinguish tumor cells from normal cells and RuPEP act as a light-emitting element to highlight breast cancer cells.
Here we designed and constructed a nanoprobe AS1411@RuPEP, and the physicochemical and biochemical properties were characterized by TEM, AFM and EDS. The breast cancer targeting diagnostic capacity was evaluated by normal/tumor cell co-culture assay, tumor cells targeting tracking in xenograft model and cancerous area selectively distinguishing in human patient tissue.
Further studies indicated that the nanoprobe exhibits excellent tumor-targeting imaging ability in vitro and in vivo by effectively recognize the over-expressed nucleolin (NCL) on the breast cancer cells membrane. Intriguingly, we discovered that the selectively enrichment of nanoprobe particles in tumor cells is related to ATP-dependent NCL transport processes that rely on the AS1411 component of nanoprobe to recognize NCL. Furthermore, preferential accumulation of nanoprobe is clearly differentiating the human breast cancer tissue surrounding non-cancerous tissue in histological analysis.
This study produce a potent nanoprobe can be used as a convenient tool to highlight and distinguish tumor cells in vivo, and indicate the tumorous grading and staging in human breast cancer patient pathological section, which provides an effective way for breast cancer diagnostic imaging by targeting recognize NCL.
具有有效成像能力的乳腺癌靶向诊断试剂对于指导肿瘤的临床方案制定、预测和疗效评估非常重要。基于 AS1411 的功能和可编程液-液相分离被 Ru(II) 配合物 RuPEP 促进的肿瘤靶向纳米探针，可能会开发成为一种潜在的磷光探针来检测乳腺癌细胞，其中 AS1411 作为肿瘤靶向导向部分，将肿瘤细胞与正常细胞区分开，RuPEP 作为发光元件，突出乳腺癌细胞。
我们设计并构建了纳米探针 AS1411@RuPEP，并通过 TEM、AFM 和 EDS 对其理化性质进行了表征。通过正常/肿瘤细胞共培养实验、异种移植模型中的肿瘤细胞靶向跟踪以及人患者组织中的癌性区域选择性区分，评估了该纳米探针的乳腺癌靶向诊断能力。
进一步的研究表明，该纳米探针通过有效识别乳腺癌细胞膜上过表达的核仁素（NCL），在体外和体内均表现出优异的肿瘤靶向成像能力。有趣的是，我们发现纳米探针颗粒在肿瘤细胞中的选择性富集与依赖于纳米探针的 AS1411 成分识别 NCL 的 ATP 依赖性 NCL 转运过程有关。此外，在组织学分析中，纳米探针的优先积累清楚地区分了人乳腺癌组织周围的非癌组织。
本研究产生了一种有效的纳米探针，可作为一种方便的工具，用于在体内突出和区分肿瘤细胞，并指示人乳腺癌患者病理切片中的肿瘤分级和分期，为通过靶向识别 NCL 进行乳腺癌诊断成像提供了一种有效方法。
