应用含奥沙利铂的温敏液体栓塞剂在兔VX2胃癌的TACE术中的应用
Application of temperature-sensitive liquid embolic agent loaded with oxaliplatin in the TACE procedure for rabbit VX2 gastric cancer.
发表日期:2023 Sep 05
作者:
Yahua Li, Xiaoyong Ge, Zongming Li, Zihe Zhou, Kunpeng Wu, Yifan Li, Tengfei Ji, Changran Wang, Kefeng Guo, Jianzhuang Ren, Xinwei Han, Kewei Ren
来源:
Drug Delivery and Translational Research
摘要:
作为一种有前途的药物输送系统,温敏性液态栓塞剂(TempSLE)在治疗胃癌方面的动物实验尚未有报道。我们观察并比较了家兔VX2胃癌模型经动脉导管化学栓塞(TACE)治疗后的计算机断层扫描(CT)成像变化、肿瘤体积、HE染色和免疫组化,以阐明TempSLE携带奥沙利铂(TempSLE/Oxa)在治疗胃癌方面的有效性。每毫升TempSLE可以携带20毫克奥沙利铂。30分钟时的累积药物释放率为38.76%,24小时后达到90%以上。TACE后1周的CT检查显示,TempSLE/Oxa组呈现无增强的低密度坏死灶,碘油携带奥沙利铂(Ioil/Oxa)组呈现肿瘤萎缩,但仍可见斑点状增强灶,而正常盐水(NS)组呈现异质性增强,肿瘤比治疗前更大。TACE术后的尸检中,TempSLE/Oxa组、Ioil/Oxa组和NS组的肿瘤体积分别为0.15±0.06 cm3、0.37±0.11 cm3和1.19±0.16 cm3,差异有统计学意义。TempSLE/Oxa组、Ioil/Oxa组和NS组的血管内皮生长因子(VEGF)和增殖细胞核抗原(PCNA)表达率差异有统计学意义,TempSLE/Oxa组最低。综上所述,TempSLE可以携带高剂量的奥沙利铂以满足临床应用需求。TempSLE/Oxa可有效抑制肿瘤细胞增殖和血管生成。本研究为TempSLE/Oxa进一步临床应用提供了实验依据。© 2023. Controlled Release Society.
As a promising drug delivery system, the temperature-sensitive liquid embolic agent (TempSLE) has yet to be reported in animal experiments in treating gastric cancer. We observed and compared computed tomography (CT) imaging changes, tumor volume, HE staining, and immunohistochemistry after transcatheter arterial chemoembolization (TACE) treatment in rabbit VX2 gastric cancer models to clarify the effectiveness of TempSLE loaded with oxaliplatin (TempSLE/Oxa) in treating gastric cancer. One milliliter TempSLE can be loaded with 20 mg oxaliplatin. The accumulative drug release rate at 30 min was 38.76%, and after 24 h, it reached more than 90%. CT examination 1 week after TACE revealed that the TempSLE/Oxa group presents unenhanced hypodense necrotic foci, the iodinated oil loaded with oxaliplatin (Ioil/Oxa) group presents shrinking tumors but still visible speckled foci of enhancement, and the normal saline (NS) group presents heterogeneous enhancement with larger tumors than before. In the postoperative autopsy of TACE, the tumor volumes of TempSLE/Oxa, Ioil/Oxa, and NS groups were 0.15 ± 0.06 cm3, 0.37 ± 0.11 cm3, and 1.19 ± 0.16 cm3, respectively, all of which were statistically different. The positive vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) expression percentages in the TempSLE/Oxa, Ioil/Oxa, and NS groups were statistically different and lowest in the TempSLE/Oxa group. In conclusion, the TempSLE can load a high dose of oxaliplatin to meet the demand of clinical applications. TempSLE/Oxa could effectively inhibit tumor cell proliferation and angiogenesis. This study provides experimental evidence for the further clinical application of the TempSLE/Oxa.© 2023. Controlled Release Society.