前列腺癌靶向磁共振成像和光热治疗的实验研究

摘要

Objective:To evaluate the application of the multifunctional nanoprobe USPION@Bn in the field of magnetic imaging (MR) and imaging-guided photothermal therapy (PTT) for prostate cancer (PCa).Methods:The probe toxicity was evaluated by MTT assays which was prepared by the covalent biocon jugation of USPION with Bn.Then MR scanning and Calcein-AM/PI staining were performed to evaluate its target imaging and photothermal ability in vitro.Then,to evaluate the MR imaging and PTT for PCa in vivo,T2WI signal intensity (SI) of the tumor area was measured by dynamic monitoring of MR after the tumor-bearing nude mice through tail intravenous injection with USPION@Bn.And after intratumor injection with USPION@Bn NPs for tumor-bearing nude mice,the first PTT with a laser (808 nm,5 W/cm2) was given,and another every 24 h,10 times totally,and was irradiated 10 min constantly every time.The control group was only irradiated without USPION@Bn NPs.Results:USPION@Bn nanoparticles were successfully prepared,and the T2WI SI of PC-3 cells significantly was reduced after co-cultured with it compared with USPION (15.36±9.13 vs 219.36±12.25,P ＜ 0.001).The apparent death of PC-3 cells was observed after co-cultured with USPION@Bn and laser irradiation.The SI value of tumor tissue of the tumorbearing nude mice decreased with the time after injection with USPION@Bn.The SI at 10 h decreased to 52％ at 0 h,and the difference was statistically significant (15.36±9.13 vs 219.36±12.25,t =12.19,P ＜ 0.001).The tumor volume in the experimental group was significantly smaller than that in the control group after laser irradiation,and the difference was statistically significant[(0.56±0.06)cm3 vs (2.39±0.11) cm3,t=-42.32,P ＜ 0.001].Conclusion:USPION@Bn can be used for PCa specific target imaging and imaging-guided photothermal therapy.%目的:制备多功能诊疗纳米探针超小超顺磁性氧化铁纳米颗粒偶联蛙皮素(USPION@Bn),并评估其用于活体前列腺癌(PCa)磁共振(MR)成像和MR介导下的光热治疗(PTT)的可行性.方法:USPION与Bn共价连接制成纳米探针USPION@Bn,并检测其毒性.MR观察对比PC-3细胞分别与USPION@Bn、USPION共培养后的增强效果.采用Calcein-AM/PI染色评估PC-3细胞与USPION@Bn共培养后经波长808 nm、功率5.0 W/cm2的激光照射5 min的PTT效果.荷人前列腺癌裸鼠模型经尾静脉注射USPION@Bn,MR监测成像效果并测量肿瘤区T2WI信号强度(SI).每天用808 nm、5.0 W/cm2的激光照射荷瘤裸鼠(实验组:经尾静脉注射USPION@Bn,对照组:仅激光照射)的肿瘤部位10 min,连续14 d,监测肿瘤体积变化.结果:成功制备出具有良好生物相容性的纳米探针USPION@Bn.其与PC-3细胞共培养后,较USPION能明显降低细胞SI(15.36±9.13 vs 219.36±12.25,P＜0.001),且在荧光显微镜下观察到具备USPION@Bn处理和激光照射的PC-3细胞出现明显的死亡.荷瘤裸鼠注射USPION@Bn后肿瘤组织的SI值随时间延长而降低,10h肿瘤区域SI下降至0h SI的52％,且两者差异具有统计学意义(381.60±41.60 vs 723.40±44.17,t=12.19,P＜0.001).活体肿瘤PTT实验显示,激光照射后实验组肿瘤体积明显小于对照组,且两者差异具有统计学意义[(0.56±0.06)cm3 vs (2.39±0.11)cm3,t=-42.32,P＜0.001].结论:USPION@Bn可作为一种有效的MR成像对比剂进行PCa的特异性靶向成像,同时可在MR成像的介导下进行体内肿瘤的PTT,抑制肿瘤的生长.