[1]张月倩,王任飞,贾强,等.131I标记共载两种靶向药物的多功能纳米载体的构建[J].国际放射医学核医学杂志,2017,41(2):88-93.[doi:10.3760/cma.j.issn.1673-4114.2017.02.002]
　Zhang Yueqian,Wang Renfei,Jia Qiang,et al.Construction of 131I-labeled and dual-drug loaded multifunctional nanoparticles[J].International Journal of Radiation Medicine and Nuclear Medicine,2017,41(2):88-93.[doi:10.3760/cma.j.issn.1673-4114.2017.02.002]
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《国际放射医学核医学杂志》[ISSN:1673-4114/CN:12-1381/R]

卷:
41
期数:
2017年第2期
页码:
88-93
栏目:
论著
出版日期:
2017-03-25

文章信息/Info

Title:
Construction of 131I-labeled and dual-drug loaded multifunctional nanoparticles
作者:
张月倩1;  王任飞1;  贾强1;  王汉杰2;  张瑞国1;  谭建1;  常津2
1. 300052 天津, 天津医科大学总医院核医学科;
2. 300072 天津, 天津大学生命科学学院
Author(s):
Zhang Yueqian1;  Wang Renfei1;  Jia Qiang1;  Wang Hanjie2;  Zhang Ruiguo1;  Tan Jian1;  Chang Jin2
1. Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin 300052, China;
2. School of Life Sciences, Tianjin University, Tianjin 300072, China
关键词:
碘放射性同位素; 二氧化硅; 纳米载体; 分子靶向药物; 甲状腺未分化癌
Keywords:
Iodine radioisotopes; Silicon dioxide; Nanoparticles; Molecular targeted drugs; Anaplastic thyroid cancer
DOI:
10.3760/cma.j.issn.1673-4114.2017.02.002
摘要:
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。
Abstract:
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<0.01) 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.

参考文献/References:

[1] Akaishi J, Sugino K, Kitagawa W, et al. Prognostic factors and treatment outcomes of 100 cases of anaplastic thyroid carcinoma[J]. Thyroid, 2011, 21(11):1183-1189. DOI:10. 1089/thy. 2010. 0332.
[2] Haugen BR, Alexander EK, Bible KC, et al. 2015 American thyroid association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer:the American thyroid association guidelines task force on thyroid nodules and differentiated thyroid cancer[J]. Thyroid, 2016, 26(1):1-133. DOI:10. 1089/thy. 2015. 0020.
[3] Kim SH, Kang JG, Kim CS, et al. 17-Allylamino-17-demethoxygeldanamycin and herbimycin a induce cell death by modulating β-catenin and PI3K/AKT signaling in FRO anaplastic thyroid carcinoma cells[J]. Anticancer Res, 2015, 35(10):5453-5460.
[4] Sadowski SM, Boufraqech M, Zhang L, et al. Torin2 targets dysregulated pathways in anaplastic thyroid cancer and inhibits tumor growth and metastasis[J]. Oncotarget, 2015, 6(20):18038-18049. DOI:10. 18632/oncotarget. 3833.
[5] He Q, Ma M, Wei C, et al. Mesoporous carbon@silicon-silica nanotheranostics for synchronous delivery of insoluble drugs and luminescence imaging[J]. Biomaterials, 2012, 33(17):4392-4402. DOI:10. 1016/j. biomaterials. 2012. 02. 056.
[6] Ickenstein LM, Edwards K, Sjöberg S, et al. A novel 125I-labeled daunorubicin derivative for radionuclide-based cancer therapy[J]. Nucl Med Biol, 2006, 33(6):773-783. DOI:10.1016/j.nucmedbio. 2006. 06. 002.
[7] Smith N, Nucera C. Personalized therapy in patients with anaplastic thyroid cancer:targeting genetic and epigenetic alterations[J]. J Clin Endocrinol Metab, 2015, 100(1):35-42. DOI:10. 1210/jc. 2014-2803.
[8] Rui M, Xin Y, Li R, et al. Targeted biomimetic nanoparticles for synergistic combination chemotherapy of paclitaxel and doxorubicin[J]. Mol Pharm, 2017, 14(1):107-123. DOI:10. 1021/acs. molpharmaceut. 6b00732.
[9] Zolata H, Afarideh H, Davani FA. Triple therapy of HER2+ cancer using radiolabeled multifunctional iron oxide nanoparticles and alternating magnetic field[J]. Cancer Biother Radiopharm, 2016, 31(9):324-329. DOI:10. 1089/cbr. 2016. 2068.
[10] 刘金剑, 张玉民, 杨翠红, 等. 酸敏感阿霉素前药纳米粒的合成及其在治疗脑胶质瘤中的作用[J]. 天津医药, 2016, 44(1):33-37. DOI:10. 11958/20150109. Liu JJ, Zhang YM, Yang CH, et al. Synthesis of acid-sensitive doxorubicin prodrug nanoparticle and its application in brain glioma treatment[J]. Tianjin Med J, 2016, 44(1):33-37.
[11] 闫岩, 王玉记, 吴建辉, 等. 17-AAG聚氰基丙烯酸正丁酯纳米粒的制备及抗肿瘤活性研究[J]. 首都医科大学学报, 2015, 36(2):178-184. DOI:10. 3969/j. issn. 1006-7795. 2015. 02. 005. Yan Y, Wang YJ, Wu JH, et al. Construction and studies on anticancer activity of 17-AAG poly-butylcyanoacrylate nanoparticles[J]. J Capit Univ Med Sci, 2015, 36(2):178-184.
[12] Li W, Liu Z, Li C, et al. Radionuclide therapy using 131I-labeled anti-epidermal growth factor receptor-targeted nanoparticles suppresses cancer cell growth caused by EGFR overexpression[J]. J Cancer Res Clin Oncol, 2016, 142(3):619-632. DOI:10. 1007/s00432-015-2067-2.
[13] 王任飞, 谭建, 李玮, 等. 17-AAG对转染NIS基因的未分化甲状腺癌摄碘动力学的影响[J]. 中华核医学与分子影像杂志, 2012, 32(4):281-285. DOI:10. 3760/cma. j. issn. 2095-2848. 2012. 04. 010. Wang RF, Tan J, Li W, et al. The effect of 17-AAG on iodine uptake kinetics of NIS-transfected anaplastic thyroid cancer cells[J]. Chin J Nucl Med Mol Imaging, 2012, 32(4):281-285.
[14] Ren F, Chen R, Wang Y, et al. Paclitaxel-loaded poly(n-butylcyanoacrylate) nanoparticle delivery system to overcome multidrug resistance in ovarian cancer[J]. Pharm Res, 2011, 28(4):897-906. DOI:10. 1007/s11095-010-0346-9.
[15] Jia L, Shen J, Li Z, et al. Successfully tailoring the pore size of mesoporous silica nanoparticles:exploitation of delivery systems for poorly water-soluble drugs[J]. Int J Pharm, 2012, 439(1/2):81-91. DOI:10. 1016/j. ijpharm. 2012. 10. 011.

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备注/Memo

备注/Memo:
收稿日期:2017-02-22。
基金项目:国家自然科学基金青年项目（81501510）
通讯作者:谭建,Email:tanpost@163.com
更新日期/Last Update: 2017-04-24