^(131)I-antiAFP导向载药纳米粒对肝癌移植瘤的抑制作用

Inhibitory effect ^(131)I-antiAFP McAb-DOX-BSA nanoparticles on hepatocellular carcinoma bearing nude mice

目的探讨^(131)I-anti AFP Mc Ab-DOX-BSA-NP对肝癌移植瘤的抑制和杀伤作用。方法制备^(131)I-anti AFP Mc Ab-DOX-BSA-NP;培养人肝癌细胞株BEL-7402及建立荷瘤裸鼠模型;将成瘤裸鼠模型按随机数字表法分为5组,每组6只。A组:空白对照组(生理盐水);B组:单纯^(131)I核素治疗组;C组:^(131)I-anti AFP Mc Ab治疗组;D组:^(131)I-anti AFP Mc Ab-DOX-BSA-NP治疗组;E组:anti AFP Mc AbDOX-BSA-NP治疗组。裸鼠瘤周注射治疗,DOX剂量为40μg/只,^(131)I活度0.2 m Ci/只(1 m Ci=3.7×107Bq),注射体积为0.2 mL/只。于4、9、14、20 d测量并记录各组裸鼠瘤体体积。同时分别在24、48、96、168 h对放射治疗组(B、C、D组)裸鼠进行SPECT检查。结果标记产物呈澄清溶液;p H值7.4;放射性化学纯度>99%,活度浓度3.91 m Ci/mL;在0.2 mol/L PB缓冲液中1、2、4 h放射性化学纯度分别为97.17%、97.10%、95.22%,稳定性良好。各组裸鼠治疗后肿瘤体积变化及生长抑制率比较:B、C、D、E治疗组较空白对照组肿瘤体积明显减小(P<0.05);与B、C、E组比较,D组肿瘤生长抑制率最强,差异有统计学意义(P<0.05)。SPECT检查结果显示:24 h时,B、C、D 3组瘤区放射性计数值差异无统计学意义(P>0.05);48、96、168 h时,^(131)I-anti AFP Mc Ab-DOX-BSA-NP治疗组(D组)及^(131)I-anti AFP Mc Ab治疗组(C组)放射性计数值均高于^(131)I治疗组(B组),差异均具有统计学意义(P<0.05),且随时间延长其差异性越来越显著。结论单克隆抗体免疫治疗、放射性^(131)I内照射治疗及载药纳米粒缓释化疗联合运用对肝癌移植瘤有显著抗癌效果。

Objective To determine the anti-tumor effect of 131I-antiAFP monoclonal antibody- doxorubicin-bovine serum albumin nanoparticles （131 I-antiAFP McAb-DOX-BSA-NP） on hepatocarcinoma bearing nude mice. Methods The antiAFP McAb-DOX-BSA-NP were prepared and then labelled with radio- iodine. Tumor xenograft model was established by transplanting human hepatoma BEL-7402 cells in nude mice. Then the model mice were randomly divided into 5 groups, that is, blank control group （group A, normal saline）, 1311 treatment group （group B）, 131I-antiAFP McAb treatment group （group C）, 131I-antiAFP MeAb-DOX-BSA-NP treatment group （group D） , and antiAFP McAb-DOX-BSA-NP treatment group （group E） , with 6 mice in each group. The agents were injected around the tumor mass, with per animal receiving DOX 40 Ixg and J31I 0.2 mCi in a total volume of 0.2 mL. The tumor volume was measured in 4, 9, 14 and 20 d. The nude mice in groups B, C and D treated with radionuelide were examined with SPECT in 24, 48, 96 and 196 h for radioactive counting. Results The labeled product presented as clear solution, with a pH value of 7.4, radioactive chemical purity of 〉 99% , and activity of 3.91 mCi/mL. The radioactive chemical purity became 97.17% , 97.10% and 95.22% in 1, 2 and 4 h respectively, when in the 0.2 mol/L PB buffer, which indicating good stability of the prepared nanoparticles. The tumor size was significantly smaller in the groups B, C, D and E than the group A （P 〈 0.05）. The tumor growth rate was most strongly suppressed in the group D, with obvious differences when compared with those in groups B, C and E （ P 〈 0.05）. SPECT indicated that there was no statistical difference in the radioactive count in groups B, C and I） in 24 h （P 〉 0.05） , but the counts in 48, 96 and 168 h were notably higher in the groups D and C than the group B （P 〈 0.05 ） , and the differences were more significant over time. Gonclusion Our prepared nanoparticles show significant anti-tumor effect for hepatocellular carcinoma bearing nude mice.