摘要
目的利用载氟尿嘧啶（5-FU）免疫聚乳酸（PEA）纳米微粒（NPs），观察其对严重联合免疫缺陷病（SCID）鼠人胃癌移植模型的治疗效应。方法超声乳化法合成的载5-FU的抗血管内皮生长因子（VEGF）单克隆抗体纳米微粒，建立SCID鼠人胃癌移植肿瘤模型，观察药物对高表达VEGF胃癌移植肿瘤模型的治疗效应及其不良反应。结果空白对照组、未载药空纳米微粒组、5-FU组（20mg／kg）、抗VEGF单克隆抗体-未载药空纳米微粒组、抗VEGF单克隆抗体组、载5-FU纳米微粒组、5-FU（20mg／kg）加抗VEGF单克隆抗体组及抗VEGF单克隆抗体-载5-FU纳米微粒组（20mg／kg）的抑瘤率分别为0、6．61％、24．26％、27．94％、35．29％、37．50％、39．71％和52．21％，且载5-FU的抗VEGF单克隆抗体纳米微粒组和未载药纳米微粒组的血白细胞数量及肝肾功能与空白对照组相比，差异无统计学意义（P〈0.05）；而含5-FU原药组血白细胞数量较空白对照组和抗VEGF单克隆抗体-载5-FU纳米微粒组下降34．43％和37．38％（P〈0.05）：而肝转氨酶升高93．17％和66．56％。治疗组与对照组癌细胞凋亡指数相比，以抗VEGF单克隆抗体．载5-FU纳米微粒组更为明显，差异有统计学意义（P〈0.05）；含抗VEGF抗体的实验组微血管密度明显低于含5-FU药组和对照组（P〈0.05）。结论载5-FU抗VEGF单克隆抗体纳米微粒可提高5-FU的抑瘤率，并通过抑制肿瘤的血管生成，诱导肿瘤细胞凋亡，增加疗效，有效降低5-FU的骨髓抑制和肝肾功能损害作用．是一种安全的新型药物纳米级靶向制剂。
Objective To explore the anti-tumor efficacy of anti- vascular endothelial growth factor （VEGF）McAb 5-fluorouracil （5-FU）loaded polylactic acid （PEA） nanoparticles （NPS） in human gastric carcinoma xenografts of nude mice. Methods Anti-VEGF McAb 5-FU loaded PLA NPS were made by ultrasound emulsification. Nude mice model of human gastric carcinoma xenografts was established. Therapeutic effects of drugs on human gastric carcinoma xenografts and side effects concerned were observed. Results The tumor inhibition rates of control group, nanosphere without 5- FU group, 5-FU （20 mg/kg） group, anti-VEGF McAb nanosphere without 5-FU group, anti-VEGF McAb group, nanosphere with 5-FU group, 5-FU （20 mg/kg） combined with anti-VEGF McAb group, anti-VEGF McAb 5-FU loaded nanosphere group was O, 6.61%, 24.26%, 27.94%, 35.29%, 37.50%, 39.71% and 52.21% respectively, and there were no significant differences between anti-VEGF McAb 5-FU loaded nanosphere group and nanosphere group without 5-FU in WBC count, serum alanine transferase level or creatinine level. Compared with control group and anti-VEGF McAb 5-FU loaded nanosphere group, the 5-FU group decreased by 34.43% and 37.38% respectively in WBC count （P〈0.05）, and increased by 93.17% and 66.56% respectively in alanine transferase. There were significant differences between experimental groups and control group in apoptosis index, especially between anti-VEGF McAb 5-FU loaded nanosphere group and control group（P〈0.05）. The microvessel density （MVD） of experimental groups containing anti-VEGF McAb was significantly lower than that of control group or groups containing 5-FU （P〈0.05）. Conclusion Anti-VEGF McAb 5-FU loaded nanosphere can increase the tumor inhibitory rate of 5-FU, induce apoptosis by inhibiting tumor angiogenesis with less side effect, and then enhance therapeutic effect, which indicate its potential as a novel, safe nano-tumor-targeting drug.
出处
《中华胃肠外科杂志》
CAS
2007年第5期482-485,共4页
Chinese Journal of Gastrointestinal Surgery
基金
国家自然科学基金（30670951）
广东省自然科学基金（06021322）
广州市科技攻关项目（2003Z3-E0381）：广东省科技攻关项目（2005B31211002）
关键词
氟尿嘧啶
聚乳酸
载药纳米微粒
胃肿瘤
血管生成
凋亡
5-fluorouracil
Polylactic acid
Drug loaded nanoparticles
Stomach neoplasms
Angiogenesis
Apoptosis
