mPEG-PCL纳米粒子负载汉防己甲素对小鼠肝癌腹水瘤的体内抗肿瘤疗效研究

In vivo antitumor effects of tetrandrine-loaded mPEG-PCL nanoparticles on ascites of murine hepatocellular carcinoma

目的研究负载汉防己甲素(Tet)的甲氧基聚乙二醇-聚己内酯(mPEG-PCL)两嵌段高分子纳米粒子在小鼠肝癌腹腔积液瘤中的抗肿瘤活性。方法采用开环聚合法合成mPEG-PCL两嵌段聚合物作为载体,通过乳化-挥发法使其负载Tet。将15只SPF级雄性ICR小鼠随机分为4组:对照组4只(予生理盐水0.5 ml)、Tet裸药组3只(予Tet 10 mg/kg)、空白纳米粒子组4只(予mPEG-PCL 5 mg/只)及Tet纳米粒子组4只(Tet 10 mg/kg+mPEG-PCL 5 mg/只)。每只小鼠腹腔注射H22细胞(4~6)×106,并于第2天开始按各组的处理方法给药,每天观察并记录小鼠腹围、体重及生存情况,连续观察7 d。结果给药后第6、7天,Tet纳米粒子组小鼠腹围小于Tet裸药组,差异有统计学意义(P<0.05)。给药前,各组小鼠体重差异无统计学意义(P>0.05);给药后,Tet裸药组小鼠体重大于对照组,空白纳米粒子组与Tet纳米粒子组小鼠体重小于Tet裸药组,差异均有统计学意义(P<0.05)。截至第7天实验结束,对照组仅存1只小鼠,其他3组均剩3只小鼠。结论Tet联合纳米粒子可有效治疗小鼠肝癌腹腔积液瘤,且未见明显不良反应。

Objective To investigate antitumor effects of tetrandrine(Tet)-loaded methoxypolyethylene glycol-polycaprolactone(mPEG-PCL)di-block polymeric nanoparticles(NPs)on murine bearing with hepatocellular carcinoma(HCC)ascites.Methods mPEG-PCL NPs were synthesized as vectors by ring-open polymerization with Tet loaded by o/w emulsification.Fifteen SPF male ICR mice were randomly divided into 4 groups(3-4 mice each group):control(0.5 ml saline),free Tet(10 mg/kg),empty NP(mPEG-PCL/5 mg)and Tet NP(Tet 10 mg/kg+mPEG-PCL 5 mg).(4-6)×106 H22 cells were injected intraperitoneally in to the mouse and the drugs were given according the group from the second day.The circumferences,weights,and survival were observed every day for 7 days.Results Compared with the free Tet group,murine treated with Tet-loaded NPs were observed with significantly lower circumference(P<0.05).No statistically significance was observed before the treatment(P>0.05)while the free Tet group was heavier than the control group,the empty NP as well as the Tet NP group(P<0.05).At the end point of the experiment(day 7),only 1 mouse survived while the other 3 groups had 3 mice left respectively.Conclusions Tet-loaded NPs may treat murine HCC ascites without significant adverse events occurred.