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目的探讨携抗αvβ3-整合素单抗靶向微泡对肿瘤新生血管的靶向效应。方法通过生物素桥接法制成携抗αvβ3-整合素单抗的靶向脂质微泡(MBa)、对照微泡携同型抗体脂质微泡(MBc);选取12只HepG2皮下移植瘤裸鼠模型(肿瘤组)和正常对照裸鼠(对照组),经尾静脉随机注射MBa、MBc和RGDfvV封闭10min后再注射MBa(Blocking+MBa),并行对比超声检查,测量声强度(VI)。分别取肿瘤组肿瘤组织和对照组正常骨骼肌组织行病理学和免疫组化检查。结果肿瘤组中MBa的VI值(17.43±3.30)U,较MBc的VI值(5.88±1.04)U增大近3倍,差异有统计学意义(P<0.01),应用RGDfvV封闭αvβ3-整合素后MBa的VI值降至(6.14±2.25)U,与MBc及对照组的各VI值比较差异均无统计学意义。免疫组化检查显示:肿瘤组织的新生血管内皮有大量αvβ3-整合素显色,可被RGDfvV封闭;而骨骼肌中仅有少量αvβ3-整合素显色。结论携抗αvβ3-整合素单抗的靶向微泡对肿瘤新生血管具有明显的靶向效应,有望用于肿瘤的诊断和疗效评估。
Objective To investigate the targeting effect of anti-αvβ3-integrin monoclonal antibody on tumor neovascularization. Methods The targeted lipid microvesicles (MBa) carrying anti-αvβ3-integrin monoclonal antibody were prepared by biotin bridging method, and the control microvesicles were incubated with the same antibody lipid microvesicles (MBc). Twelve HepG2 subcutaneous xenografts (Tumor group) and normal control nude mice (control group). MBa (MBa, MBc and RGDfvV) were injected into the caudal vein 10 min before injection of MBa (Blocking + MBa). Contrastive ultrasonography was performed to measure the sound intensity (VI). Tumor tissues of the tumor group and normal skeletal muscle tissue of the control group were respectively examined by pathology and immunohistochemistry. Results The value of MBa in tumor group was (17.43 ± 3.30) U, which was nearly 3 times higher than that of MBc (5.88 ± 1.04) U, the difference was statistically significant (P <0.01). RGDfvV was used to block αvβ3-integrin The VI value of MBa decreased to (6.14 ± 2.25) U, and there was no significant difference between each VI value of MBa and the control group. Immunohistochemical examination showed that a large amount of αvβ3-integrin was found in the neovascular endothelium of tumor tissues and could be blocked by RGDfvV. However, only a small amount of αvβ3-integrin was observed in skeletal muscle. Conclusion The targeted microbubbles carrying anti-αvβ3-integrin monoclonal antibody have obvious targeting effects on tumor neovascularization and are expected to be used in the diagnosis and therapeutic evaluation of tumors.