Ren Kewei, Li Yahua, Zhou Zihe, Wu Kunpeng, Wang Jianan, Yao Jianning, Li Yifan, Ge Xiaoyong, Li Xiao, Li Zhen, Li Zongming, Han Xinwei
Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Engineering Technology Research Center for Minimally Invasive Interventional Tumors of Henan Province, Zhengzhou, Henan, China.
Front Oncol. 2023 Jul 19;13:1153759. doi: 10.3389/fonc.2023.1153759. eCollection 2023.
Bevacizumab loaded drug-eluting beads have the potential to reduce TACE related VEGF expression. The purpose of this study was to investigate the in vitro loading, and release profiles of bevacizumab (BEV) loaded on Callispheres beads (CB) and its application in rabbit liver VX tumor model.
CB with sizes of 100-300 um and 300-500 um were divided into 5 groups, respectively. BEV with different content was prepared for CB loading, releasing and detected in the solution at different time points. The diameters of CB in each group were measured under a light microscope to calculate the shrinkage rate. The rabbit with VX2 liver model were divided into control group, CB-TACE group, CB-TACE+BEV group, and BEV group. The data of blood test, CT image, HE and IHC staining were compared and analyzed.
The shrinkage rate of the 100-300 um CB was 2.6-7.2%, while the 300-500 um CB was 0.2-7.1%. The BEV-loaded CB (BEV-CB) has a burst release during the first hour and following gradually released with time. The release profiles of 100-300 um CB reach 34% in 24 hours, while the 300-500 um CB to 25.8%. BEV-CB with sizes of 100-300 um was chosen to perform transcatheter arterial chemoembolization (TACE). The results showed that BEV-CB-TACE not only gradually increased the content of BEV in serum and organ tissue but also reduced the level of VEGF in serum. Pathological results suggested that the expression of HIF-1 was elevated while VEGF and MVD decreased when compared to the other groups.
In conclusion, this study confirms that Callispheres beads could efficiency loaded BEV. BEV-CB-TACE has a good safety and effectiveness, and its application could reduce the level of VEGF-A in serum in the treatment of VX tumors.
载有贝伐单抗的药物洗脱微球有潜力降低经动脉化疗栓塞（TACE）相关的血管内皮生长因子（VEGF）表达。本研究的目的是调查贝伐单抗（BEV）负载于载药微球（CB）上的体外负载及释放情况，以及其在兔肝VX肿瘤模型中的应用。
将粒径为100 - 300微米和300 - 500微米的CB分别分为5组。制备不同含量的BEV用于CB负载、释放，并在不同时间点检测溶液中的情况。在光学显微镜下测量每组CB的直径以计算收缩率。将VX2肝模型兔分为对照组、CB-TACE组、CB-TACE+BEV组和BEV组。对血液检测、CT图像、苏木精-伊红（HE）染色和免疫组化（IHC）染色的数据进行比较和分析。
100 - 300微米CB的收缩率为2.6 - 7.2%，而300 - 500微米CB为0.2 - 7.1%。载有BEV的CB（BEV-CB）在第1小时有突发释放，随后随时间逐渐释放。100 - 300微米CB在24小时内的释放率达到34%，而300 - 500微米CB为25.8%。选择粒径为100 - 300微米的BEV-CB进行经导管动脉化疗栓塞（TACE）。结果显示，BEV-CB-TACE不仅使血清和器官组织中BEV的含量逐渐增加，还降低了血清中VEGF的水平。病理结果表明，与其他组相比，缺氧诱导因子-1（HIF-1）的表达升高，而VEGF和微血管密度（MVD）降低。
总之，本研究证实载药微球能有效负载BEV。BEV-CB-TACE具有良好的安全性和有效性，其应用可降低VX肿瘤治疗中血清VEGF-A的水平。
