State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Colloids Surf B Biointerfaces. 2019 Jul 1;179:56-65. doi: 10.1016/j.colsurfb.2019.03.049. Epub 2019 Mar 23.
One hallmark of solid tumors, regardless of its type or stage, is the existence of an unsual acidic microenvironment, which has been considered a specific and ideal target for cancer imaging. Therefore, we developed a pH-activatable nanoprobe GNPs-CKL-FA for near-infrared fluorescence (NIR) and computed tomography (CT) imaging of tumors. This nanoprobe consists of a near-infrared fluorophore (Cy5.5), a pH-sensitive ketal linker, and gold nanoparticles (GNPs) decorated with folates that could bind to tumor cells' surface receptors to promote cellular internalization. This ability of folate to mediate tumor targeting and accelerate internalization has been confirmed by in vitro experiments with HeLa cells. The fluorescence of the nanoprobes successfully activated by low intracellular pH, especially in more acidic organelles. Furthermore, fluorescence signals increased to a greater extent when the pH in tumors was lowered by injection of acetate buffer and isoproterenol. The CT contrast of GNPs-CKL-FA was obtained after administering intravenously to HeLa subcutaneous tumor-bearing mice. These results suggest that GNPs-CKL-FA has the potential to be a pH-activatable fluorescent nanoprobe combined with CT contrast agent for tumor targeted imaging.
无论肿瘤类型或阶段如何，实体瘤的一个标志是存在异常酸性的微环境，这已被认为是癌症成像的特定和理想靶点。因此，我们开发了一种用于肿瘤近红外荧光（NIR）和计算机断层扫描（CT）成像的 pH 激活型纳米探针 GNPs-CKL-FA。该纳米探针由近红外荧光团（Cy5.5）、pH 敏感的缩酮连接子和金纳米粒子（GNPs）组成，GNPs 上修饰有叶酸，可与肿瘤细胞表面受体结合，促进细胞内化。用 HeLa 细胞进行的体外实验证实了叶酸介导肿瘤靶向和促进内化的能力。纳米探针在低细胞内 pH 下成功激活的荧光，特别是在更酸性的细胞器中。此外，当通过注射醋酸盐缓冲液和异丙肾上腺素降低肿瘤中的 pH 时，荧光信号增加到更大程度。静脉注射到荷 HeLa 皮下肿瘤的小鼠后，获得了 GNPs-CKL-FA 的 CT 对比。这些结果表明，GNPs-CKL-FA 有可能成为一种 pH 激活型荧光纳米探针，与 CT 造影剂结合，用于肿瘤靶向成像。
