Li Cong, Greenwood Tiffany R, Glunde Kristine
JHU ICMIC Program, The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Neoplasia. 2008 Apr;10(4):389-98. doi: 10.1593/neo.07856.
Noninvasive imaging of lysosomes will be useful 1) to elucidate the role of lysosomal parameters in cancer, 2) to diagnose malignant lesions, and 3) to evaluate future lysosome-targeted anticancer therapies. Lysosome-specific labeling of glucosamine-bound near-infrared (NIR) fluorescent probes, IR-1 and IR-2, but not control probe IR-15 without the glucosamine moiety, was observed by fluorescence microscopy in human breast epithelial cell lines. Lysosome labeling and tumor specificity of these NIR probes were investigated by dynamic optical imaging and immunofluorescence staining in human breast tumor xenografts. IR-1 and IR-2 demonstrated faster lysosome labeling rates in highly aggressive MDA-MB-231 and MDA-MB-435 cells compared with less aggressive MCF-7 and nontumorigenic MCF-12A cells. IR-1 and IR-2, but not IR-15, accumulated in human MDA-MB-231, MDA-MB-435, and MCF-7 breast tumor xenografts in vivo. IR-2 demonstrated the highest maximum fluorescence and tumor/normal tissue ratios in all tumor models. Specific lysosome labeling from IR-2 in vivo was validated by colocalization of the NIR fluorescence with CD63 immunofluorescence in tumor sections. IR-1 and IR-2 demonstrated high lysosome-labeling ability and breast tumor-targeting specificity in vitro and in vivo. They are promising for diagnosing malignant lesions and may provide a means for evaluating and monitoring future lysosome-targeted anticancer therapies.
1）阐明溶酶体参数在癌症中的作用；2）诊断恶性病变；3）评估未来针对溶酶体的抗癌疗法。通过荧光显微镜在人乳腺上皮细胞系中观察到，与不含氨基葡萄糖部分的对照探针IR-15不同，氨基葡萄糖结合的近红外（NIR）荧光探针IR-1和IR-2具有溶酶体特异性标记。通过动态光学成像和免疫荧光染色，在人乳腺肿瘤异种移植模型中研究了这些NIR探针的溶酶体标记和肿瘤特异性。与侵袭性较低的MCF-7和非致瘤性MCF-12A细胞相比，IR-1和IR-2在高侵袭性的MDA-MB-231和MDA-MB-435细胞中表现出更快的溶酶体标记率。IR-1和IR-2而非IR-15在人MDA-MB-231、MDA-MB-435和MCF-7乳腺肿瘤异种移植模型中在体内蓄积。在所有肿瘤模型中，IR-2表现出最高的最大荧光强度和肿瘤/正常组织比率。通过肿瘤切片中NIR荧光与CD63免疫荧光的共定位，验证了IR-2在体内的特异性溶酶体标记。IR-1和IR-2在体外和体内均表现出高溶酶体标记能力和乳腺肿瘤靶向特异性。它们在诊断恶性病变方面具有潜力，并且可能为评估和监测未来针对溶酶体的抗癌疗法提供一种手段。
