Preparation and biodistribution of 188Re-labeled folate conjugated human serum albumin magnetic cisplatin nanoparticles (188Re-folate-CDDP/HSA MNPs) in vivo.
Preparation and biodistribution of 188Re-labeled folate conjugated human serum albumin magnetic cisplatin nanoparticles (188Re-folate-CDDP/HSA MNPs) in vivo.
复制标题
188Re标记叶酸缀合人血清白蛋白磁性顺铂纳米颗粒(188Re-folate-CDDP/HSA MNPs)的制备及其体内生物分布
DOI：
10.2147/ijn.s24322
复制
发表时间：
2011
影响因子：
8
通讯作者：
Guo CQ
中科院分区：
文献类型：
--
作者：
Tang QS;Chen DZ;Xue WQ;Xiang JY;Gong YC;Zhang L;Guo CQ
背景本研究的目的是开发基于磁流体热疗、纳米颗粒包裹的顺铂化疗和磁性白蛋白颗粒的腹腔热疗。此外，为了结合高温靶向治疗、化疗和放疗的多重杀伤作用，白蛋白纳米颗粒表面与放射性核素188Re标记的叶酸配体（188Re-叶酸-CDDP/HSA）连接。方法采用预锡法，用188Re标记人血清白蛋白。研究了反应时间和最佳标记条件。将颗粒静脉注射到小鼠体内，并在不同时间点处死小鼠。在重要器官中测量注射剂量百分比（％ID/g）的每克组织的放射性。评估了 188Re-叶酸-CDDP/HAS 磁性纳米颗粒的生物分布。结果 188Re标记叶酸结合白蛋白与顺铂磁性纳米粒子结合的最佳条件为：0.1 mL葡萄糖酸钠溶液（0.3 mol/L）、0.1 mL溶解氯化亚锡的浓盐酸（10 mg/mL）、0.04 mL乙酸缓冲溶液（pH 5，0.2 mol/L）、30 mg叶酸结合白蛋白与顺铂磁性纳米颗粒和 188ReO4 洗脱液 (0.1 mL) 结合。 188Re-叶酸-CDDP-HSA磁性纳米粒子形成率超过90%，放射化学纯度超过95%。 37°C 小牛血清中的总体标记率为 83%。裸鼠注射188Re-叶酸-CDDP/HSA磁性纳米粒子后，主要摄取组织为肝脏、肾脏、肠道和肿瘤。体内188Re-叶酸-CDDP/HSA磁性纳米粒子的摄取在注射后逐渐增加，在8小时达到峰值，值为8.83±1.71，并在24小时内缓慢下降。结论这些结果表明188Re-叶酸-CDDP/HSA磁性纳米粒子可用于放射性核素靶向癌症治疗。成功制备了叶酸配体标记放射性核素（188Re）表面修饰的白蛋白纳米颗粒，为热疗、化疗、放射治疗的三重杀伤作用奠定了基础。
Background The purpose of this study was to develop intraperitoneal hyperthermic therapy based on magnetic fluid hyperthermia, nanoparticle-wrapped cisplatin chemotherapy, and magnetic particles of albumin. In addition, to combine the multiple-killing effects of hyperthermal targeting therapy, chemotherapy, and radiotherapy, the albumin-nanoparticle surfaces were linked with radionuclide 188Re-labeled folic acid ligand (188Re-folate-CDDP/HSA). Methods Human serum albumin was labeled with 188Re using the pre-tin method. Reaction time and optimal conditions of labeling were investigated. The particles were intravenously injected into mice, which were sacrificed at different time points. Radioactivity per gram of tissue of percent injected dose (% ID/g) was measured in vital organs. The biodistribution of 188Re-folate-CDDP/HAS magnetic nanoparticles was assessed. Results Optimal conditions for 188Re-labeled folate-conjugated albumin combined with cisplatin magnetic nanoparticles were: 0.1 mL of sodium gluconate solution (0.3 mol/L), 0.1 mL of concentrated hydrochloric acid with dissolved stannous chloride (10 mg/mL), 0.04 mL of acetic acid buffer solution (pH 5, 0.2 mol/L), 30 mg of folate-conjugated albumin combined with cisplatin magnetic nanoparticles, and 188ReO4 eluent (0.1 mL). The rate of 188Re-folate-CDDP-HSA magnetic nanoparticle formation exceeded 90%, and radiochemical purity exceeded 95%. The overall labeling rate was 83% in calf serum at 37°C. The major uptake tissues were the liver, kidney, intestine, and tumor after the 188Re-folate-CDDP/HSA magnetic nanoparticles were injected into nude mice. Uptake of 188Re-folate-CDDP/HSA magnetic nanoparticles increased gradually after injection, peaked at 8 hours with a value of 8.83 ± 1.71, and slowly decreased over 24 hours in vivo. Conclusion These results indicate that 188Re-folate-CDDP/HSA magnetic nanoparticles can be used in radionuclide-targeted cancer therapy. Surface-modified albumin nanoparticles with folic acid ligand-labeled radionuclide (188Re) were successfully prepared, laying the foundation for a triple-killing effect of thermotherapy, chemotherapy, and radiation therapy.