Cao Xiao-Cheng, Mao Xue-Li, Lu Shan-Shan, Zhu Wei, Huang Wei, Yi Hong, Yuan Li, Zhou Jian-Hua, Xiao Zhi-Qiang
Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, China.
Research Center of Carcinogenesis and Targeted Therapy, Xiangya Hospital, Central South University, Changsha 410008, China.
ACS Omega. 2024 Oct 17;9(43):43826-43833. doi: 10.1021/acsomega.4c06761. eCollection 2024 Oct 29.
PD-L1 is an immune checkpoint molecule mediating cancer immune escape, and its expression level in the tumor has been used as a biomarker to predict response to immune checkpoint inhibitor (ICI) therapy. Our previous study reveals that an 11 amino acid-long ANXA1-derived peptide (named A11) binds and degrades the PD-L1 protein in multiple cancers and is a potential peptide for cancer diagnosis and treatment. Near-infrared fluorescence (NIF) optical imaging of tumors offers a noninvasive method for detecting cancer and monitoring therapeutic responses. In this study, an NIF dye Cy5.5 was conjugated with A11 peptide to develop a novel PD-L1-targeted probe for molecular imaging of tumors and monitor the dynamic changes in PD-L1 expression in tumors. imaging studies showed that intense fluorescence was observed in triple-negative breast cancer MDA-MB-231, nonsmall cell lung cancer H460, and melanoma A375 cells incubated with Cy5.5-A11, and the cellular uptake of Cy5.5-A11 was efficiently inhibited by coincubation with unlabeled A11 or knockdown of cellular PD-L1 by shRNA. imaging studies showed accumulation of Cy5.5-A11 in the MDA-MB-231, H460, and A375 xenografts with good contrast from 0.5 to 24 h after intravenous injection, indicating that Cy5.5-A11 possesses the strong ability for tumor imaging. Moreover, the fluorescent signal of A11-Cy5.5 in the xenografts was successfully blocked by coinjection of unlabeled A11 peptide or knockdown of cellular PD-L1 by shRNA, indicating the specificity of Cy5.5-A11 targeting PD-L1 in tumor imaging. Our data demonstrate that Cy5.5-A11 is a novel tool for tumor imaging of PD-L1, which has the potential for detecting cancer and predicting ICI therapeutic responses.
程序性死亡配体1（PD-L1）是一种介导癌症免疫逃逸的免疫检查点分子，其在肿瘤中的表达水平已被用作预测免疫检查点抑制剂（ICI）治疗反应的生物标志物。我们之前的研究表明，一种由11个氨基酸组成的膜联蛋白A1（ANXA1）衍生肽（命名为A11）在多种癌症中结合并降解PD-L1蛋白，是一种潜在的癌症诊断和治疗肽。肿瘤的近红外荧光（NIF）光学成像为检测癌症和监测治疗反应提供了一种非侵入性方法。在本研究中，将一种近红外染料Cy5.5与A11肽偶联，开发出一种新型的靶向PD-L1的探针，用于肿瘤的分子成像并监测肿瘤中PD-L1表达的动态变化。成像研究表明，在用Cy5.5-A11孵育的三阴性乳腺癌MDA-MB-231、非小细胞肺癌H460和黑色素瘤A375细胞中观察到强烈荧光，并且通过与未标记的A11共孵育或用短发夹RNA（shRNA）敲低细胞PD-L1可有效抑制Cy5.5-A11的细胞摄取。成像研究表明，静脉注射后0.5至24小时，Cy5.5-A11在MDA-MB-231、H460和A375异种移植瘤中蓄积，对比度良好，表明Cy5.5-A11具有很强的肿瘤成像能力。此外，通过共注射未标记的A11肽或用shRNA敲低细胞PD-L1成功阻断了异种移植瘤中A11-Cy5.5的荧光信号，表明Cy5.5-A11在肿瘤成像中靶向PD-L1的特异性。我们的数据表明，Cy5.5-A11是一种用于PD-L1肿瘤成像的新型工具，具有检测癌症和预测ICI治疗反应的潜力。
