Visualization of nonsmall-cell lung cancer by near-infrared fluorescence imaging with tumor-targeting peptide ABT-510

被引:0
|
作者
Tu, Yuanbiao [1 ]
Gao, Minfang [1 ]
Tao, Tianming [1 ]
Zhou, Kuncheng [1 ]
Li, Shuxin [1 ]
Tao, Ji [3 ]
Wang, Fang [1 ]
Han, Ray P. S. [1 ]
Chen, Ziliang [1 ]
Li, Gang [2 ]
Luo, Ping [1 ]
机构
[1] Jiangxi Univ Chinese Med, Canc Res Ctr, Jiangxi Engn Res Ctr Translat Canc Technol, Jiangxi Prov Key Lab Diag Treatment & Rehabil Canc, Nanchang 330004, Peoples R China
[2] Yuzhang Normal Univ, Dept Ecol & Environm, Key Lab Nanchang City Green New Mat & Ind Wastewat, Nanchang 330103, Peoples R China
[3] Fudan Univ, Human Phenome Inst, Shanghai 201203, Peoples R China
基金
中国国家自然科学基金;
关键词
Nonsmall-cell lung cancer; Orthotopic tumour; Liver metastasis; Intestinal metastases; Near-infrared fluorescence imaging; PHASE-I; METASTASES; MODEL; SURVIVAL; GROWTH;
D O I
10.1016/j.bioorg.2024.107685
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Nonsmall-cell lung cancer (NSCLC) is the most frequent type of lung cancer, with early surgical treatment proving vital for prolonged patient survival. However, precise visualization of NSCLC remains a challenge due to limited molecular imaging probes, the unique anatomical structure of the lungs, and respiratory movement interference. In this study, we investigated the potential utility of CD36, which is highly expressed in NSCLC, as an imaging target. A selective and water-soluble fluorescent probe, MPA-ABT-510, was successfully constructed by coupling ABT-510 with MPA, a near-infrared (NIR) fluorescent dye. Molecular docking analysis shows that MPA-ABT-510 possesses strong binding affinity to the CD36 protein, with specific hydrogen bond interactions at defined amino acid residues. In vitro assays reveals that the fluorescein isothiocyanate-labeled peptide ABT-510 specifically binds to the CD36-high expressing NSCLC cell lines H1299 and A549. In vivo imaging verifies that the MPA-ABT-510 efficiently accumulates in the tumor site with a distinct fluorescent signal. Ex vivo imaging revealed that tumor-to-lung fluorescence ratios for subcutaneous and orthotopic H1299 mouse models were 7.19 f 0.73 and 1.91 f 0.42, respectively, while those for A549 mice were 5.53 f 0.64 and 1.77 f 0.41, respectively. Biodistribution analysis demonstrated efficient MPA-ABT-510 uptake in H1299 and A549 liver metastases models with tumor-to-liver fluorescence ratios of 2.47 f 0.48 and 2.19 f 0.22, respectively. High MPA-ABT-510 accumulation was evident in A549 intestinal metastases models, as evidenced by tumor-to-colorectal fluorescence ratios of 4.27 f 0.11. MPA-ABT-510 exhibits superior imaging capabilities with minimal safety concerns, so it is a promising candidate for NSCLC surgical navigation.
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页数:11
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