131I标记共载两种靶向药物的多功能纳米载体的构建

目的构建131I标记的、共载17-丙烯胺基-17-去甲氧基格尔德霉素（17-AAG）与Torin2两种分子靶向性药物的新型多功能介孔二氧化硅（mSiO₂）纳米载体，测定其表征，了解其释药动力学，以及甲状腺未分化癌（ATC）细胞对其摄取的情况。方法采用传统的模板法制作mSiO₂，按照浓度比为1:1的比例装载两种靶向药物17-AAG与Torin2，并在其表面进行氨基化修饰后连接胎牛血清白蛋白（BSA），测定其基本表征、药物的载药量及包封率。采用高效液相色谱法分析纳米载体所载药物的体外释放情况。采用氯胺T法对纳米载体进行131I标记，测定其标记率及放化纯度。通过核素胞内摄取定量实验了解该纳米载体被ATC细胞的摄取及滞留情况。采用SPSS19.0统计学软件，对数据进行独立样本t'检验。结果成功制备mSiO₂并完成装载（17-AAG+Torin2）@mSiO₂-BSA-131I纳米载体，经测定得到两者的有效直径分别约为170~250 nm和200~300 nm，并证实所得纳米载体的分散性好且具有理想的球形形态。131I标记率为66.31%~78.25%，放化纯度为98.80%~99.42%，mSiO₂对17-AAG及Torin2的载药量分别为（7.31±0.22）%和（6.04±0.79）%，包封率分别为（86.21±1.32）%和（85.17±2.05）%。证实所得纳米载体对17-AAG与Torin2均具有一定的缓释效果。ATC细胞内核素摄取定量实验结果显示（17-AAG+Torin2）@mSiO₂-BSA-131I可被细胞快速摄取且于3 h时达摄取高峰，其细胞摄碘量明显高于Na131I溶液，差异有统计学意义（t=32.63~109.31，均P < 0.01）。结论mSiO₂纳米载体可以实现两种靶向药物的共载及131I的标记，且具有一定的药物缓释作用，ATC细胞能够明显、快速地摄取（17-AAG+Torin2）@mSiO₂-BSA-131I。

Construction of 131I-labeled and dual-drug loaded multifunctional nanoparticles

Objective To construct 131I-labeled and dual-drug-loaded multifunctional mesoporous silica(mSiO2) nanoparticles,and to investigate its characteristics,drug release kinetics,and uptake by anaplastic thyroid cancer(ATC) cells.Methods The mSiO2 nanoparticles were constructed through the conventional template method.17-allylamino-17-demethoxygeldanamycin(17-AAG) and Torin2 were loaded at equal concentrations,and bovine serum albumin was connected to the amino-modified nanoparticles.The characteristics,encapsulation efficiency,and drug loading rates of the nanoparticles were then investigated.Drug release was analyzed by high-performance liquid chromatography.The nanoparticles were labeled with 131I using the chloramine-T method.The time-dependent cellular uptake of 131I-labeled nanoparticles was also analyzed to evaluate the uptake and retention of the nanoparticles in ATC cells.T'-test was used for data analysis using SPSS19.0 software.Results The mSiO2 nanoparticles and (17-AAG+Torin2)@mSiO2-BSA-131I samples were successfully constructed.The average diameters were 170 nm to 250 nm and 200 nm to 300 nm,respectively,with good dispersibility and spherical shape.The labeling rate and radiochemical purity of the 131I-nanoparticles were 66.31％ to 78.25％ and 98.80％ to 99.42％,respectively.The drug loading rates of 17-AAG and Torin2 were 7.31％±0.22％ and 6.04％±0.79％,and their encapsulation efficiencies were 86.21％±1.32％ and 85.17％±2.05％,respectively.The nanoparticles loaded with 17-AAG and Torin2 exhibited slow drug release behavior.The uptake of(17-AAG+Torin2)@mSiO2-BSA-131I was higher than that of Na131I(t=32.63-109.31,all P＜O.01) and could reach its maximum level at 3 h after incubation.Conclusions The mSiO2 nanoparticles loaded with 17-AAG and Torin2 and labeled with 131I exhibited slow drug release behavior.ATC cells could uptake(17-AAG+Torin2)@mSiO2-BSA-131I rapidly.