Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College , Huazhong University of Science and Technology , Wuhan , 430030 , People's Republic of China.
Bioconjug Chem. 2018 Dec 19;29(12):4119-4126. doi: 10.1021/acs.bioconjchem.8b00756. Epub 2018 Dec 5.
Molecular imaging agents are considered to be promising tracers for tumor imaging and guided therapy. TMTP1 was screened through the FliTrx bacterial peptide display system in our laboratory previously and shown to specifically target to primary tumors and metastatic foci. In this study, small peptide TMTP1 was designed to conjugate to a near-infrared fluorescent agent ICG derivative ICG-OSu through PEG4, forming the novel probe TMTP1-PEG4-ICG. It was successfully synthesized and certified. CCK-8 assay showed that it was nontoxic to normal cells and cancerous cells. Dynamics study indicated that the probe was cleared through the liver-intestine and kidney-bladder pathway. Tumor targeting capability of this probe in vitro was evaluated on 4T1, SiHa, HeLa, S12, and HaCaT cells by flow cytometry. In vivo imaging of 4T1 and HeLa tumor-bearing mice further identified the tumor homing ability. As we had expected, the probe showed excellent affinity to cancer cells not only in vitro but also in vivo, whether in murine tumor or humanized tumor. In conclusion, TMTP1-PEG4-ICG demonstrated ideal imaging effects on tumor-bearing mice model, providing new opportunities for tumor diagnostic or guiding resection.
分子成像剂被认为是肿瘤成像和引导治疗有前途的示踪剂。TMTP1 是我们实验室以前通过 FliTrx 细菌肽展示系统筛选出来的，它被证明可以特异性地靶向原发性肿瘤和转移性病灶。在这项研究中，小肽 TMTP1 通过 PEG4 与近红外荧光剂 ICG 衍生物 ICG-OSu 偶联，形成新型探针 TMTP1-PEG4-ICG。它已经成功地被合成并得到了验证。CCK-8 试验表明，它对正常细胞和癌细胞均无毒性。动力学研究表明，该探针通过肝肠和肾膀胱途径清除。通过流式细胞术，在 4T1、SiHa、HeLa、S12 和 HaCaT 细胞上评估了该探针在体外的肿瘤靶向能力。4T1 和 HeLa 荷瘤小鼠的体内成像进一步确定了该探针的肿瘤归巢能力。正如我们所预期的，该探针不仅在体外，而且在体内（无论是在鼠肿瘤还是人源化肿瘤中），均表现出对癌细胞的优异亲和力。总之，TMTP1-PEG4-ICG 在荷瘤小鼠模型上表现出理想的成像效果，为肿瘤的诊断或指导切除提供了新的机会。
