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整合素αvβ3受体在某些肿瘤细胞和肿瘤新生血管表达上调,可以作为受体阳性表达的肿瘤的示踪靶点。本研究利用近红外荧光染料Cy5.5标记一种新型肽(命名为P1c)构建的分子探针(Cy5.5-P1c),对高表达整合素αvβ3受体的人乳腺癌MDA-MB-231裸鼠肿瘤模型进行在体及体外近红外光学成像研究。流式细胞术及激光共聚焦显微镜结果显示P1c能够与MDA-MB-231细胞特异性结合。活体近红外荧光成像显示Cy5.5-P1c探针在肿瘤部位有明显的积聚,且肿瘤对探针的摄取能被游离的P1c阻断;离体肿瘤组织的荧光强度明显高于其它正常组织;免疫组织化学结果提示肿瘤组织对Cy5.5-P1c探针的摄取与整合素αvβ3受体阳性表达有关。以上结果提示,P1c有希望成为疾病治疗中药物传递的载体,有助于肿瘤定位的研究。
The integrin αvβ3 receptor is up-regulated in some tumor cells and tumor neovascularization, which can be used as a target of tracking of receptor-positive tumors. In this study, a molecular probe (Cy5.5-P1c) constructed by labeling of a novel peptide (named P1c) with a near-infrared fluorescent dye Cy5.5 was used to detect the expression of integrin αvβ3 in human breast cancer MDA-MB-231 Nude mice tumor model in vitro and in vivo studies of near infrared optical imaging. Flow cytometry and laser confocal microscopy showed that P1c could specifically bind to MDA-MB-231 cells. In Vivo near-infrared fluorescence imaging showed that Cy5.5-P1c probe had a significant accumulation in the tumor site, and the uptake of the probe by the tumor was blocked by the free P1c. The fluorescence intensity of the in vitro tumor tissue was significantly higher than that of other normal tissues. Immunohistochemical results suggested that tumor tissue uptake of Cy5.5-P1c probe was related to the positive expression of integrin αvβ3 receptor. The above results suggest that P1c hopefully become a carrier of drug delivery in disease treatment and contribute to the study of tumor localization.