FTS与NIRF共轭化合物用于小鼠肿瘤模型的成像和治疗

目的 研究法尼基硫代水杨酸（farnesylthiosalicylic Acid，FTS）与七甲川菁（heptamethine carbocyanine）近红外（near infrared，NIR）荧光染料共轭化合物的肿瘤靶向性及其在活体成像中的应用，明确该化合物对肿瘤生长的抑制作用。方法 将人乳腺癌细胞MCF-7、胶质瘤细胞U251和前列腺癌细胞PC3培养至对数生长期后，分别加入不同浓度的FTS和FTS-IR783，观察两种化合物对肿瘤细胞的生长抑制作用；培养的三种肿瘤细胞中加入FTS-IR783（20 μmol/L），荧光显微镜下观察荧光染料在肿瘤细胞中的聚集；将三种肿瘤细胞（每只1×10⁶个）皮下移植裸鼠，两周后荷瘤鼠腹腔注射FTS-IR783（每只10 nmol/L），活体成像分别测定肿瘤部位近红外荧光信号和肿瘤体积的相关性。结果 与FTS相比较，FTS-IR783可显著抑制MCF-7、U251和PC3的生长；三种肿瘤细胞可特异性识别FTS-IR783，呈现近红外荧光集聚；皮下荷瘤模型注射FTS-IR783后，活体成像显示肿瘤部位荧光强度与生物发光强度相关性分别达到0.987，0.998和0.971。结论 FTS与近红外荧光染料IR-783共轭结合后可特异性识别肿瘤细胞，用于肿瘤模型的活体成像，同时该化合物具有的肿瘤靶向性可显著抑制肿瘤细胞的生长，有望成为新型的靶向药物。

Application of FTS and NIRF conjugated compounds in imaging and therapy of mouse tumor models

Objective To study the tumor targeting ability and application of farnesylthiosalicylic Acid (FTS) and heptamethine carbocyanine fluorescent dye-mediated near-infrared imagine in living animals, and confirm the inhibitory effect of this compound on growth of tumor cells. Methods Human breast cancer cell line MCF-7, glioma cell line U251 and prostate cancer cell line PC3 were cultured to logarithmic growth phase, and different concentrations of FTS and FTS-IR783 were added, respectively. We observed the inhibitory effect of those two compounds on the growth of tumor cells. Under fluorescence microscopy, specific accumulation of FTS-IR783 in these tumor cells was observed. The tumor cells (1×10⁶) were transplanted subcutaneously into nude mice. These mice were subjected to intraperitoneal injection of FTS-IR783 (10 nmol/mouse) two weeks later. In the in vivo imaging, near infrared fluorescence signal and tumor volume were measured and their correlation was analyzed. Results Compared with FTS, FTS-IR783 significantly inhibited the growth of MCF-7, U251 and PC3 cells in vitro. FTS-IR783 was specifically uptaken by these three kinds of tumor cells, showing strong near infrared fluorescence in cell agglomerates. After subcutaneous injection of FTS-IR783, the correlation between fluorescence intensity and tumor volume was 0.987, 0.998 and 0.971, respectively. Conclusions The compound of FTS conjugated with near infrared fluorescent dye IR-783 can specifically recognize tumor cells, in both in vitro and in vivo imaging. At the same time, the compound can significantly inhibit the growth of tumor cells, and may be expected to become a new potential targeted drug.