Kong Xiaohan, Sun Yangwen, Zhang Qian, Li Siju, Jia Yizhen, Li Rui, Liu Yang, Xie Zhiyong
School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou 510275, China.
ACS Omega. 2022 May 17;7(21):18073-18084. doi: 10.1021/acsomega.2c01494. eCollection 2022 May 31.
Detection of circulating tumor cells (CTCs) could be widely used for early diagnosis and real-time monitoring of tumor progression in liquid biopsy samples. Compared with normal cells, tumor cells exhibit relatively strong negative surface charges due to the high rate of glycolysis. In this study, a cationic fluorescence "turn-on" aggregation-induced emission (AIE) nanoprobe based on gold nanorods (GNRs) was designed and tested to detect tumor cells specifically. In brief, tetraphenylethene (TPE), an AIE dye, was conjugated to the cationic polymer polyethylenimine (PEI) yielding TPEI. TPEI-PEG-SH was obtained by further functionalizing TPEI with a thiol group. TPEI-PEG-SH was grafted to the surface of GNRs, yielding the cationic AIE nanoprobe, named as GNRs-PEG-TPEI. The nanoprobe was characterized to have a uniform particle size of 172 nm, a strong positive surface charge (+54.87 mV), and a surface modification load of ∼40%. The stability of GNRs-PEG-TPEI was verified. The cellular imaging results demonstrated that the nanoprobe could efficiently recognize several types of tumor cells including MCF-7, HepG2, and Caco-2 while exhibiting specific fluorescence signals only after interacting with tumor cells and minimal background interference. In addition, the study investigated the toxicity of the nanoprobe to the captured cells and proved the safety of the nanoprobe. In conclusion, a specific and efficient nanoprobe was developed for capture and detection of different types of tumor cells based on their unique metabolic characteristics. It holds great promise for achieving early diagnosis and monitoring the tumor progression by detecting the CTCs in clinical liquid biopsy samples.
循环肿瘤细胞（CTC）的检测可广泛用于液体活检样本中肿瘤的早期诊断和实时进展监测。与正常细胞相比，肿瘤细胞由于糖酵解速率高而表现出相对较强的表面负电荷。在本研究中，设计并测试了一种基于金纳米棒（GNR）的阳离子荧光“开启”聚集诱导发光（AIE）纳米探针，以特异性检测肿瘤细胞。简而言之，将AIE染料四苯乙烯（TPE）与阳离子聚合物聚乙烯亚胺（PEI）偶联，得到TPEI。通过用硫醇基团进一步功能化TPEI获得TPEI-PEG-SH。将TPEI-PEG-SH接枝到GNR表面，得到阳离子AIE纳米探针，命名为GNRs-PEG-TPEI。该纳米探针的特征在于粒径均匀，为172nm，表面正电荷较强（+54.87mV），表面修饰负载约为40%。验证了GNRs-PEG-TPEI的稳定性。细胞成像结果表明，该纳米探针能够有效识别包括MCF-7、HepG2和Caco-2在内的几种类型的肿瘤细胞，并且仅在与肿瘤细胞相互作用后才表现出特异性荧光信号，背景干扰最小。此外，该研究还考察了纳米探针对捕获细胞的毒性，并证明了纳米探针的安全性。总之，基于不同类型肿瘤细胞独特的代谢特征，开发了一种特异性和高效的纳米探针用于捕获和检测肿瘤细胞。通过检测临床液体活检样本中的CTC来实现早期诊断和监测肿瘤进展具有很大的前景。
