靶向CXCR4–CXCL12轴，用于可视化，预测和抑制治疗性AMD3100–Ag2S量子点探针的乳腺癌转移,Advanced Functional Materials

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靶向CXCR4–CXCL12轴，用于可视化，预测和抑制治疗性AMD3100–Ag2S量子点探针的乳腺癌转移
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2018-04-20 , DOI: 10.1002/adfm.201800732
Zhaohui Wang ₁ , Yi Ma ₁ , Xiyuan Yu ₁ , Qi Niu ₁ , Zhihao Han ₁ , Han Wang ₁ , Tingting Li ₁ , Dingping Fu ₁ , Samuel Achilefu ₂ , Zhiyu Qian ₃ , Yueqing Gu ₁

Affiliation

乳腺癌转移仍然是主要的死亡原因，预测和降低转移风险的努力尤其有吸引力。CXC趋化因子受体4（CXCR4）因其趋化归巢于CXCL12而被报道为特异性转移。本文中，CXCR4拮抗剂AMD3100与荧光硫化银量子点（Ag ₂S）核心（QD-AMD）可以准确检测肿瘤中CXCR4的表达。特别是，该探针可将高转移性乳腺癌细胞与转移能力较低的乳腺癌细胞区分开。纵向体内成像在早期阶段预测，高CXCR4表达原位4T1肿瘤在接种肿瘤后14 d随后会转移至肺部，而低CXCR4表达MCF-7肿瘤则无转移。相关的测量发现，肺中CXCL12的水平随着肿瘤的进展而增加。QD-AMD对肿瘤细胞上的CXCR4干扰或抗体对肺中CXCL12的干扰均成功抑制了癌症转移。在原发性4T1肿瘤模型中静脉注射QD-AMD可有效减少肺转移。更重要的是，由于固有的光热效应，转移性扩散随着原发性肿瘤的实质性缩小而被更彻底地消除。总之，该探针有望检测，预测和抑制乳腺肿瘤的转移扩散。

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Targeting CXCR4–CXCL12 Axis for Visualizing, Predicting, and Inhibiting Breast Cancer Metastasis with Theranostic AMD3100–Ag2S Quantum Dot Probe

Breast cancer metastasis remains the primary cause of death and efforts to predict and reduce metastatic risk are particularly appealing. CXC chemokine receptor 4 (CXCR4) is reported as a specific metastasis due to its chemotactic homing to CXCL12. Herein, conjugation of a CXCR4 antagonist, AMD3100, to a fluorescent silver sulfide quantum dot (Ag₂S) core (QD‐AMD) allows accurate detection of CXCR4 expression in tumor. Particularly, the probe precisely distinguishes highly metastatic breast cancer cells from those of lower metastatic ability. Longitudinal in vivo imaging predicts at early stages that the high CXCR4 expressing orthotopic 4T1 tumor would subsequently metastasize to lungs 14 d after tumor inoculation, while no metastasis forms from the low CXCR4 expressing MCF‐7 tumor. Correlative measurements find that the CXCL12 levels in lung increase with tumor progression. Perturbations of either CXCR4 on tumor cells by QD‐AMD or CXCL12 in the lungs by antibody successfully inhibit cancer metastasis. Intravenous injection of QD‐AMD in primary 4T1 tumor model effectively reduces lung metastasis. More importantly, due to the intrinsic photothermal effect, the metastatic spread is more thoroughly abrogated along with substantial shrinkage of primary tumor. Altogether, the probe is promising to detect, predict, and inhibit the metastatic spread of breast tumor.

更新日期：2018-04-20

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