Molecular Science and Biomedicine Laboratory, College of Chemistry and Chemical Engineering, State Key Laboratory of Chemo/Biosensing and Chemometrics, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha 410082, China.
Molecular Science and Biomedicine Laboratory, College of Chemistry and Chemical Engineering, State Key Laboratory of Chemo/Biosensing and Chemometrics, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha 410082, China.
Talanta. 2017 Dec 1;175:421-426. doi: 10.1016/j.talanta.2017.04.081. Epub 2017 May 1.
Alkaline phosphatase (ALP), one of the important hydrolases, is associated with the progress of many diseases as a well-defined biomarker. Fluorescence imaging of ALP in living organisms is of great importance for biological studies. However, in vivo detection of ALP remains a great challenge because current fluorescent probes show short excitation and emission wavelength, which are not desired for in vivo fluorescence imaging. Herein we reported a near-infrared (NIR) fluorescent probe (NALP) for turn-on trapping of ALP activity in living cancer cells and tumors. NALP was composed of a NIR-emitting fluorophore as a reporter and phosphate as a triggered moiety. Phosphate group was directly tethered to the hydroxyl group of fluorophore, which prohibited the fluorescence. The probe exhibited a high selectivity and remarkable fluorescence turn-on response to ALP in aqueous solutions with a detection limit of 0.28U/L. Benefiting from NIR excitation and emission, high contrast on the imaging signal could be achieved in response to endogenous ALP activity. Impressively, not only we successfully used NALP for imaging of endogenous ALP activity in cancer cells, but also, applied it for fluorescence imaging of ALP in tumor tissues and living tumor xenograft in nude mice for the first time. The probe was expected to be promising tool for practical application in disease diagnosis on the roles of ALP in disease.
碱性磷酸酶（ALP）是一种重要的水解酶，作为一种明确的生物标志物，与许多疾病的进展有关。在活生物体中对 ALP 的荧光成像对于生物学研究非常重要。然而，由于当前的荧光探针具有较短的激发和发射波长，因此在活体内检测 ALP 仍然是一个巨大的挑战，这不利于体内荧光成像。在此，我们报道了一种近红外（NIR）荧光探针（NALP），用于在活癌细胞和肿瘤中开启型捕获 ALP 活性。NALP 由近红外发射荧光团作为报告基团和磷酸酯作为触发基团组成。磷酸酯基团直接连接到荧光团的羟基上，从而阻止了荧光。该探针在水溶液中对 ALP 具有高选择性和显著的荧光开启响应，检测限为 0.28U/L。受益于近红外激发和发射，能够实现对内源性 ALP 活性的成像信号的高对比度。令人印象深刻的是，我们不仅成功地使用 NALP 对癌细胞内源性 ALP 活性进行了成像，而且还首次将其应用于肿瘤组织和裸鼠体内肿瘤异种移植中的 ALP 荧光成像。该探针有望成为在疾病诊断中实际应用的有前途的工具，可用于研究 ALP 在疾病中的作用。
