The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510500, People's Republic of China.
State Key Laboratory of Chemical Biology and Drug Discovery, and Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, People's Republic of China.
Int J Nanomedicine. 2019 Jun 13;14:4309-4317. doi: 10.2147/IJN.S201722. eCollection 2019.
The intraoperative visualization of tumor cells is a powerful modality for surgical treatment of solid tumors. Since the completeness of tumor excision is closely correlated with the survival of patients, probes that can assist in distinguishing tumor cells are highly demanded. In the present study, a fluorescent probe JF1 was synthesized for imaging of tumor cells by conjugating a substrate of cathepsin B (quenching moiety) to Oregon Green derivative JF2 using a self-immolative linker. JF1 was then loaded into the folate-PEG modified CaCO nanoparticles. The folate receptor-targeted, pH-dependent, and cathepsin B activable CaCO nanoprobe was test in vitro and in vivo for tumor imaging. CaCO nanoprobe demonstrated good stability and fast lighting ability in tumors under low pH conditions. It also showed lower fluorescence background than the single cathepsin B dependent fluorescent probe. The pH-dependent and cathepsin B controlled "turn-on" property enables precise and fast indication of tumor in vitro and in vivo. This strategy of controlled drug delivery enables in vivo imaging of tumor nodules with a high signal-to-noise ratio, which has great potential in surgical tumor treatment.
肿瘤细胞的术中可视化是实体瘤手术治疗的一种强大手段。由于肿瘤切除的完整性与患者的生存密切相关，因此非常需要能够协助区分肿瘤细胞的探针。在本研究中，通过使用自耗竭连接子将组织蛋白酶 B 的底物（猝灭部分）连接到 Oregon Green 衍生物 JF2 上，合成了用于肿瘤细胞成像的荧光探针 JF1。然后将 JF1 载入叶酸-PEG 修饰的 CaCO 纳米颗粒中。研究了靶向叶酸受体、pH 依赖性和组织蛋白酶 B 激活的 CaCO 纳米探针在体外和体内的肿瘤成像。在低 pH 条件下，CaCO 纳米探针在肿瘤中表现出良好的稳定性和快速的点亮能力。它还显示出比单一组织蛋白酶 B 依赖性荧光探针更低的荧光背景。这种 pH 依赖性和组织蛋白酶 B 控制的“开启”特性使体外和体内的肿瘤能够进行精确和快速的指示。这种控制药物递送的策略能够对肿瘤结节进行高信噪比的体内成像，这在肿瘤手术治疗中具有很大的潜力。
