Targeting Fluorescent Nanodiamonds to Vascular Endothelial Growth Factor Receptors in Tumor.
Targeting Fluorescent Nanodiamonds to Vascular Endothelial Growth Factor Receptors in Tumor.
复制标题
将荧光纳米金刚石靶向肿瘤中的血管内皮生长因子受体。
DOI：
10.1021/acs.bioconjchem.8b00803
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发表时间：
2019
影响因子：
4.7
通讯作者：
Shenderova,OlgaA
中科院分区：
文献类型：
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作者：
Torelli,MarcoD;Rickard,AshlynG;Backer,MarinaV;Filonov,DariaS;Nunn,NicholasA;Kinev,AlexanderV;Backer,JosephM;Palmer,GregoryM;Shenderova,OlgaA
血管内皮生长因子（VEGF）及其受体的表达增加与生长中的肿瘤中的血管生成相关，通过靶向示踪剂的方式为肿瘤选择性成像提供潜在靶点。虽然荧光示踪剂用于靶向体内成像，但目前许多荧光团缺乏光稳定性和生物相容性，阻碍了它们在涉及长期连续成像的几种应用中的使用。为了解决这些问题，荧光纳米金刚石（FND），表现出无限的光稳定性和优异的生物相容性，被探索作为示踪剂中的荧光团，用于靶向生长中的肿瘤中的VEGF受体。为了探索FND用于肿瘤VEGF受体成像的效用，我们使用点击化学将多个拷贝的用反式环辛烯（scVEGF-TCO）位点特异性衍生的工程化单链形式的VEGF缀合至140 nm FND。然后通过生化和组织培养实验测试所得靶向缀合物FND-scVEGF的scVEGF部分的功能活性，并在患有诱导的4 T1癌的Balb/c小鼠中测试选择性肿瘤摄取。我们发现，FND-scVEGF缀合物在细胞培养实验中保持对VEGF受体的高亲和力，并且观察到FND-scVEGF相对于非靶向FND在肿瘤中的优先积累。显微光谱法通过氮空位诱导荧光的独特光谱形状提供了组织内FND的明确测定。这些结果验证并邀请将靶向FND用于诊断成像，并鼓励进一步优化FND的荧光亮度。
The increased expression of vascular endothelial growth factor (VEGF) and its receptors is associated with angiogenesis in a growing tumor, presenting potential targets for tumor-selective imaging by way of targeted tracers. Though fluorescent tracers are used for targetedin vivoimaging, the lack of photostability and biocompatibility of many current fluorophores hinder their use in several applications involving long-term, continuous imaging. To address these problems, fluorescent nanodiamonds (FNDs), which exhibit infinite photostability and excellent biocompatibility, were explored as fluorophores in tracers for targeting VEGF receptors in growing tumors. To explore FND utility for imaging tumor VEGF receptors, we used click-chemistry to conjugate multiple copies of an engineered single-chain version of VEGF site-specifically derivatized withtrans-cyclooctene (scVEGF-TCO) to 140 nm FND. The resulting targeting conjugates, FND-scVEGF, were then tested for functional activity of the scVEGF moieties through biochemical and tissue culture experiments and for selective tumor uptake in Balb/c mice with induced 4T1 carcinoma. We found that FND-scVEGF conjugates retain high affinity to VEGF receptors in cell culture experiments and observed preferential accumulation of FND-scVEGF in tumors relative to untargeted FND. Microspectroscopy provided unambiguous determination of FND within tissue by way of the unique spectral shape of nitrogen-vacancy induced fluorescence. These results validate and invite the use of targeted FND for diagnostic imaging and encourage further optimization of FND for fluorescence brightness.