^(131)I标记金属有机框架材料对失分化甲状腺癌治疗的体内研究

I labeled metal-organic framework materials for the treatment of dedifferentiated thyroid carcinoma in vivo

目的拟构建一种多功能锆基有机框架材料(Zr-MOF),实现对失分化甲状腺癌的精准治疗。方法 Zr-MOF@^(131)I复合体的制备,Zr-MOF@^(131)I对甲状腺裸鼠移植瘤生长的影响,免疫组织化学检测肿瘤组织内凋亡因子及HIF-1α的表达含量,蛋白印迹实验检测HIF-1α的表达含量。结果通过对比不同治疗组对裸鼠移植瘤生长的影响,可见Zr-MOF@^(131)I组的鼠肿瘤体积和重量较对照组变化最大(P<0.01),与其余两组比较有统计学差异(P<0.05);免疫组化结果显示Zr-MOF@^(131)I组凋亡较对照组明显(P<0.01),较其余组比较有统计学差异(P<0.05);免疫组化和蛋白印迹结果均显示Zr-MOF@^(131)I组肿瘤组织的乏氧状态改善较其余组均有统计学差异(P<0.05);四组裸鼠的体重并未发现明显的统计学差异(P>0.05)。结论 Zr-MOF@^(131)I可以明显抑制失分化甲状腺癌裸鼠移植瘤的生长,^(131)I标记多功能纳米材料为有效治疗失分化甲状腺癌提供了新技术。

Objective To construct a multifunctional zirconium-based organic framework material(Zr-MOF) to achieve precise treatment of dedifferentiated thyroid cancer. Methods The preparation of ^(131)I-labeled multifunctional Zr-MOF complex, the effect of Zr-MOF@^(131)I on the growth of transplanted thyroid tumor in nude mice. The expression of apoptotic factors and HIF-1α in tumor tissues were detected by immunohistochemistry, and the protein expression of HIF-1α was detected by Western blot. Results By comparing the treatment effects of different groups on the growth of xenograft tumor in nude mice, it was found that the tumor volume and weight of the Zr-MOF@^(131)I group decreased significantly compared with the control group(P<0.01), and significantly different from the ^(131)I group and Zr-MOF group(P<0.05). The survival curve of the nude mice in the Zr-MOF@^(131)I group was significantly longer than that in the other groups(P<0.05). Immunohistochemical results showed that the apoptosis of Zr-MOF@^(131)I group was significantly increased compared with the control group(P<0.01), and the difference was statistically significant compared with other groups(P<0.05). Both immunohistochemical and Western blot results indicated that the hypoxia state of tumor tissues in the Zr-MOF@^(131)I group was improved most significantly compared with the other groups(P<0.05). There was no statistically significant difference in body weight between the four groups(P>0.05). Conclusion Zr-MOF@^(131)I can significantly inhibit the growth of the transplanted tumor in nude mice with dedifferentiated thyroid carcinoma. The ^(131)I labeled multifunctional nanomaterials in this study can provide a new technology and strategy for the effective treatment of dedifferentiated thyroid cancer.