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中华普通外科学文献(电子版) ›› 2023, Vol. 17 ›› Issue (03) : 173 -177. doi: 10.3877/cma.j.issn.1674-0793.2023.03.003

论著

近红外二区新型血管内皮生长因子受体靶向探针在结直肠癌小鼠模型中的应用
王博, 白子锐, 李坚()   
  1. 519000 珠海,中山大学附属第五医院肝胆外科与肝移植科
  • 收稿日期:2023-04-03 出版日期:2023-06-01
  • 通信作者: 李坚
  • 基金资助:
    国家自然科学基金项目(82272105、81971773); 广东省基础与应用基础研究基金项目(2022A1515011244)

Preparation of a novel VEGFR-targeting probe second near-infrared window in a mouse model of colorectal cancer

Bo Wang, Zirui Bai, Jian Li()   

  1. Department of Hepatobiliary Surgery and Liver Transplantation, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China
  • Received:2023-04-03 Published:2023-06-01
  • Corresponding author: Jian Li
引用本文:

王博, 白子锐, 李坚. 近红外二区新型血管内皮生长因子受体靶向探针在结直肠癌小鼠模型中的应用[J]. 中华普通外科学文献(电子版), 2023, 17(03): 173-177.

Bo Wang, Zirui Bai, Jian Li. Preparation of a novel VEGFR-targeting probe second near-infrared window in a mouse model of colorectal cancer[J]. Chinese Archives of General Surgery(Electronic Edition), 2023, 17(03): 173-177.

目的

探讨近红外二区(NIR-Ⅱ,1 000~1 700 nm)新型血管内皮生长因子受体(VEGFR)靶向探针ICG-PEG5000-Bev在肠癌小鼠模型中的成像效果,为其在结直肠癌及肝转移的应用前景提供依据。

方法

利用ICG-PEG5000-NHS和贝伐珠单抗制备NIR--Ⅱ新型VEGFR靶向探针ICG-PEG5000-Bev,验证其光谱表征和生物安全性,进一步利用NIR-Ⅱ成像设备观察探针对CT-26-luc肠癌小鼠在体成像。

结果

ICG-PEG5000-Bev具有良好的生物安全性,光谱实验证明其具有NIR-Ⅱ成像能力,且在一定范围内随着探针溶液质量浓度的升高,荧光强度线性增强。成像实验说明ICG-PEG5000-Bev能够实现CT-26-luc肠癌小鼠模型的在体成像,且具有比NIR--Ⅰ更低的背景信号强度。

结论

ICG-PEG5000-Bev可实现结直肠癌小鼠模型的在体检测,且生物安全性良好,具有较强的临床转化价值。

Objective

To investigate the imaging effect of the second near-infrared window (NIR-Ⅱ, 1 000-1 700 nm), a novel VEGFR-targeting probe ICG-PEG5000-Bev in a mouse model of colorectal cancer.

Methods

ICG-PEG5000-Bev, a novel VEGFR-targeting probe in NIR-Ⅱ region, was prepared to verify its spectral characterization and biosafety. The in vivo imaging effect and application prospect of ICG-PEG5000-Bev was further explored by using the NIR-Ⅱ imaging device in mice model with CT-26-luc colorectal cancer.

Results

ICG-PEG5000-Bev had good biological safety. Spectral experiments showed that it had NIR-Ⅱ imaging ability, and the fluorescence intensity increased linearly with the increase of probe solution concentration within a certain range. The NIR-Ⅱ imaging effect of the probe showed that ICG-PEG5000-Bev could achieve in vivo imaging of mice with colorectal cancer, with lower background signal strength than NIR-Ⅰ .

Conclusion

ICG-PEG5000-Bev can be used to detect colorectal cancer in mice in vivo with good biosafety and strong clinical transformation value.

图1 ICG-PEG5000-Bev合成路径
图2 ICG-PEG5000-Bev光谱表征和粒径分析 A为激发光谱;B为探针在NIR-Ⅰ/Ⅱ谱段范围内的激发光谱;C为粒径分布曲线
图3 ICG-PEG5000-Bev荧光强度随浓度变化关系 A为50 mW/cm2激光照射下不同溶液浓度NIR-Ⅱ成像伪彩图;B为探针质量浓度和荧光强度的变化曲线
图4 探针ICG-PEG5000-Bev在CT-26-luc皮下移植瘤模型NIR-Ⅰ成像
图5 CT-26-luc皮下移植瘤模型NIR-Ⅰ肿瘤区域平均荧光强度
图6 探针ICG-PEG5000-Bev在CT-26-luc皮下移植瘤模型NIR-Ⅱ成像
图7 CCK8实验验证ICG-PEG5000-Bev体外细胞毒性
图8 苏木精-伊红染色验证ICG-PEG5000-Bev在体组织毒性(×10)
[1]
Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249.
[2]
Siegel RL, Miller KD, Goding Sauer A, et al. Colorectal cancer statistics, 2020[J]. CA Cancer J Clin, 2020, 70(3): 145-164.
[3]
中华人民共和国国家卫生健康委员会. 中国结直肠癌诊疗规范(2020版)[J]. 中华消化外科杂志, 2020, 19(6): 563-88.
[4]
中国医师协会结直肠肿瘤专业委员会, 中国抗癌协会大肠癌专业委员会, 国家癌症中心国家肿瘤质控中心结直肠癌质控专家委员会. 结直肠癌靶向治疗中国专家共识[J/CD]. 中华普通外科学文献(电子版), 2023, 17(1): 1-8.
[5]
Margonis GA, Sergentanis TN, Ntanasis-Stathopoulos I, et al. Impact of surgical margin width on recurrence and overall survival following R0 hepatic resection of colorectal metastases: A systematic review and meta-analysis[J]. Ann Surg, 2018, 267(6): 1047-1055.
[6]
Hamady ZZ, Lodge JP, Welsh FK, et al. One-millimeter cancer-free margin is curative for colorectal liver metastases: A propensity score case-match approach[J]. Ann Surg, 2014, 259(3): 543-548.
[7]
Lauwerends LJ, van Driel P, Baatenburg de Jong RJ, et al. Real-time fluorescence imaging in intraoperative decision making for cancer surgery[J]. Lancet Oncol, 2021, 22(5): e186-e195.
[8]
Smith AM, Mancini MC, Nie S. Bioimaging: second window for in vivo imaging[J]. Nat Nanotechnol, 2009, 4(11): 710-711.
[9]
Goi T, Fujioka M, Satoh Y, et al. Angiogenesis and tumor proliferation/metastasis of human colorectal cancer cell line SW620 transfected with endocrine glands-derived-vascular endothelial growth factor, as a new angiogenic factor[J]. Cancer Res, 2004, 64(6): 1906-1910.
[10]
Freire Valls A, Knipper K, Giannakouri E, et al. VEGFR1+ metastasis-associated macrophages contribute to metastatic angiogenesis and influence colorectal cancer patient outcome[J]. Clin Cancer Res, 2019, 25(18): 5674-5685.
[11]
Boogerd L, Hoogstins C, Schaap DP, et al. Safety and effectiveness of SGM-101, a fluorescent antibody targeting carcinoembryonic antigen, for intraoperative detection of colorectal cancer: A dose-escalation pilot study[J]. Lancet Gastroenterol Hepatol, 2018, 3(3): 181-191.
[12]
de Gooyer JM, Elekonawo F, Bremers A, et al. Multimodal CEA-targeted fluorescence and radioguided cytoreductive surgery for peritoneal metastases of colorectal origin[J]. Nat Commun, 2022, 13(1): 2621.
[13]
Li F, Zhang Z, Cai J, et al. Primary preclinical and clinical evaluation of (68)Ga-DOTA-TMVP1 as a novel VEGFR-3 PET imaging radiotracer in gynecological cancer[J]. Clin Cancer Res, 2020, 26(6): 1318-1326.
[14]
Fleetwood F, Klint S, Hanze M, et al. Simultaneous targeting of two ligand-binding sites on VEGFR2 using biparatopic affibody molecules results in dramatically improved affinity[J]. Sci Rep, 2014, 4: 7518.
[15]
Hu Z, Fang C, Li B, et al. First-in-human liver-tumour surgery guided by multispectral fluorescence imaging in the visible and near-infrared-Ⅰ/Ⅱ windows[J]. Nat Biomed Eng, 2020, 4(3): 259-271.
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