目的 考察前药叶酸-牛血清白蛋白-氟尿嘧啶偶联物(叶酸-BSA-5-Fu)纳米粒在荷瘤小鼠的体内分布特征及药效。方法 建立H₂₂肝癌细胞实体瘤模型小鼠，考察了叶酸-BSA-5-Fu纳米粒3个剂量组（高、中、低）对荷瘤小鼠肿瘤生长情况的影响，并与牛血清白蛋白-5-氟尿嘧啶偶联物(BSA-5-Fu)纳米粒组， 叶酸阻断组（游离叶酸+叶酸-BSA-5-Fu纳米粒），5-氟尿嘧啶组及阴性生理盐水对照组进行比较。采用荧光分光光度法研究腹腔注射给药后包裹钙黄绿素实验组在体内的分布情况。 结果 腹腔注射叶酸-BSA-5-Fu纳米粒高剂量组的荷瘤小鼠肿瘤生长最为缓慢，抑瘤率最高，叶酸-BSA-5-Fu纳米粒的抑瘤率高于BSA-5-Fu纳米粒，在加入1 mmol·L-1外源性叶酸后，叶酸-BSA-5-Fu纳米粒的抑瘤率明显降低。5-Fu-sol 的抑瘤率高于BSA-5-Fu纳米粒，体内分布实验结果表明，包裹钙黄绿素叶酸-BSA-5-Fu纳米粒在肿瘤的分布高于包裹钙黄绿素BSA-5-Fu纳米粒。结论 叶酸-牛血清白蛋白-氟尿嘧啶偶联物是一种有潜力的抗肿瘤的前体药物，可靶向于高表达叶酸受体的肿瘤。

OBJECTIVE To investigate the distribution in vivo and pharmacodynamics of prodrug folate-bovine serum albumin-5-fluorouracil nanoparticles in mice．METHODS The H₂₂ hepatoma cells solid tumor mouse model was established. The effect of Folate-BSA-5-Fu nanoparticles (high， medium and low) on tumor growth conditions in the tumor-bearing mice were studied，and compared with bovine serum albumin-5-fluorouracil (BSA-5-Fu) nanoparticles group， folate blocking group (free folate+folate-BSA-5-Fu nanoparticles)， positive 5-fluorouracil group and negative saline group.After intraperitoneal injection, the distribution of experimental group loaded calcein nanoparticles were determined by fluorospectrophotometry.RESULTS The tumor growth in tumor-bearing mice was the slowest in high dose folate-BSA-5-Fu nanoparticles group. The inhibition rate was the highest after intraperitoneal injection. The inhibition rate of folate-BSA-5-Fu nanoparticles were higher than that of BSA-5-Fu nanoparticles. After coadministration of 1 mmol·L-1 exogenous folate， the inhibition rate of folate-BSA-5-Fu nanoparticles were decreased significantly. The inhibition rate of 5-Fu-sol was higher than that of BSA-5-Fu nanoparticles. The distribution content in vivo of folate-BSA-5-Fu loaded calcein nanoparticles were higher than that of BSA-5-Fu loaded calcein nanoparticles.CONCLUSION Folate - bovine serum albumin-5 - fluorouracil was a potential anti-tumor prodrug and it can be targeted at the high expression of folate receptor tumor.