Liu Xiao, Gong Xiangyang, Yuan Jie, Fan Xiaopeng, Zhang Xingxing, Ren Tianbing, Yang Sheng, Yang Ronghua, Yuan Lin, Zhang Xiao-Bing
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, PR China.
Hunan Provincial Key Laboratory of Cytochemistry, School of Chemistry and Food Engineering, Changsha University of Science and Technology, Changsha 410114, PR China.
Anal Chem. 2021 Apr 6;93(13):5420-5429. doi: 10.1021/acs.analchem.0c04804. Epub 2021 Mar 22.
Tumor-specific imaging is a major challenge in clinical tumor resection. To overcome this problem, several activatable probes have been developed for use in tumor imaging. However, most of these probes are activated based on a single-factor stimulation and are irreversible. Therefore, false signals that make tumor-specific imaging difficult are easily generated. We have developed a new dual-stimulus responsive near-infrared (NIR) reversible adenosine 5'-triphosphate (ATP)-pH probe for fluorescence and photoacoustic ratiometric imaging of tumors. Since the H and ATP content is significantly higher in the tumor microenvironment than that in normal tissues, the Förster resonance energy transfer-based probe ATP-pH was constructed with silicon rhodamine as the donor, CS dye as the acceptor, and ATP/H recognition units that could only be activated when both H and ATP were connected to the acceptor. The ATP-pH probe is reversibly activated by both the H and ATP, which effectively reduces the cumulative response of the probe in circulation after intravenous injection. Further, the NIR ratiometric property of the probe makes it suitable for imaging. Finally, our probe was successfully utilized in ratiometric photoacoustic and fluorescence tumor imaging and ratiometric fluorescence imaging-guided tumor resection.
肿瘤特异性成像在临床肿瘤切除中是一项重大挑战。为克服这一问题,已开发出几种可激活探针用于肿瘤成像。然而,这些探针大多基于单因素刺激激活且不可逆。因此,容易产生使肿瘤特异性成像困难的假信号。我们开发了一种新型双刺激响应近红外(NIR)可逆三磷酸腺苷(ATP)-pH探针,用于肿瘤的荧光和光声比率成像。由于肿瘤微环境中的氢离子和ATP含量显著高于正常组织,基于Förster共振能量转移构建了ATP-pH探针,以硅罗丹明为供体,CS染料为受体,并带有仅在氢离子和ATP都连接到受体时才能激活的ATP/氢离子识别单元。ATP-pH探针可被氢离子和ATP可逆激活,有效降低了静脉注射后探针在循环中的累积响应。此外,该探针的近红外比率特性使其适用于成像。最后,我们的探针成功用于比率光声和荧光肿瘤成像以及比率荧光成像引导的肿瘤切除。
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