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一种用于肿瘤图像引导手术和转移追踪的氨肽酶N可激活化学发光探针。

An aminopeptidase N-activatable chemiluminescence probe for image-guided surgery and metastasis tracking of tumor.

作者信息

Shi Xiang, Deng Yu, Liu Xiaoyang, Gao Ge, Wang Rui, Liang Gaolin

机构信息

State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, Jiangsu, 210096, China.

State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, Jiangsu, 210096, China.

出版信息

Biosens Bioelectron. 2022 Jul 15;208:114212. doi: 10.1016/j.bios.2022.114212. Epub 2022 Mar 31.

Abstract

Malignant tumors are a severe threat to human health. Surgical removal is still the preferred method in clinical practice among the many treatment strategies. Nevertheless, tiny residual tumor lesions and distant metastases are always missed during surgery, resulting in tumor recurrence. Therefore, it is important for doctors to distinguish residual tumor tissues and distant metastases from normal tissues but remains challenging. Herein, we rationally designed an aminopeptidase-activatable chemiluminescence (CL) probe Ala-PD to distinguish cancer tissues from normal tissues through a spraying manner. In vitro studies revealed that Ala-PD could specifically respond to APN with a ∼26-fold CL signal turn-on ratio and a limit of detection of 0.531 ng/mL. Moreover, Ala-PD exhibited an ultrahigh tumor-to-normal tissue CL ratio of above 1.2 × 10. Furthermore, the ability of Ala-PD to image metastatic tumor tissues was also achieved in tumor-bearing mouse, highlighting the potential of Ala-PD to be applied in image-guided surgery clinically.

摘要

恶性肿瘤对人类健康构成严重威胁。在众多治疗策略中,手术切除仍是临床实践中的首选方法。然而,手术过程中总是会遗漏微小的残留肿瘤病灶和远处转移灶,导致肿瘤复发。因此,对医生来说,将残留肿瘤组织和远处转移灶与正常组织区分开来很重要,但仍然具有挑战性。在此,我们合理设计了一种氨肽酶可激活的化学发光(CL)探针Ala-PD,通过喷涂方式区分癌组织和正常组织。体外研究表明,Ala-PD能对氨肽酶N(APN)产生特异性反应,化学发光信号开启率约为26倍,检测限为0.531 ng/mL。此外,Ala-PD的肿瘤与正常组织化学发光比值超高,超过1.2×10。此外,Ala-PD在荷瘤小鼠中也实现了对转移性肿瘤组织成像的能力,突出了Ala-PD在临床图像引导手术中应用的潜力。

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