新型多模态硅质体纳米分子探针的在体研究

摘要

目的 制备新型的双模态显像硅质体纳米分子探针,并评估其在动物体内的分布和药代动力学特性.方法 利用硅质体纳米材料包载ICG制成纳米探针,硅质体表面修饰连接螯合剂DOTA,并用111 In标记.标记后的硅质体111 In-ICG-DPDCs通过尾静脉注射到正常小白鼠体内,在给药后不同时间点处死并取血及感兴趣脏器,评价其药代动力学特性和体内分布情况.建立荷路易士肺癌(LLC)C57BL/6黑鼠皮下肿瘤模型,用小动物IVIS和SPECT对荷瘤鼠进行活体成像,观察肿瘤部位对硅质体探针的摄取情况.结果 硅质体纳米材料包载ICG制成纳米探针的粒径约为90 nm,成功偶联DOTA后用111 In标记,纯化后的放化纯为99.93%.标记后的硅质体体外稳定性良好,纯化后48 h放化纯为97.10%.该硅质体血液循环时间较长,快速半衰期为4.0 min,慢速半衰期为132.7 min;主要聚集在肝脏和脾脏,且滞留时间较长.NanoScanSPECT/CT显像示LLC肿瘤在注射后4 h有明显摄取,肝脾亦摄取较高,与生物分布结果一致.光学成像示肿瘤对探针有明显摄取,与SPECT显像结果一致.结论 设计的硅质体探针能用于肿瘤SPECT和光学双模态显像.%Objective To prepare a novel dual-modality imaging probe based on Cerasome nano-materials, and evaluate its in vivo biodistribution and pharmacokinetic properties. Methods ICG encapsu-lated Cerasome was modified with chelating agent DOTA for 111 In-labeling. Normal mice firstly were used for in vivo studies. Animals were sacrificed at different time points after tail vein administration, blood samples were taken and the organs of interest were captured to evaluate the pharmacokinetic properties and in vivo biodistribution of 111 In-ICG-DPDCs. The subcutaneous Lewis lung carcinoma ( LLC ) tumor model in C57BL/6 mouse was established. The tumor-bearing mice were subjected to optical imaging in small animal IVIS and SPECT imaging in small animal nanoScanSPECT/CT system for tumor uptake of 111 In-ICG-DPDCs. Results The size of the nanoparticle probe was about 90 nm, and the 111 In-labeling was successfully per-formed with 99.93% radiochemical purity after purification. 111 In-ICG-DPDCs showed excellent in vitro sta-bility with 97.10% radiochemical purity at 48 h post-purification. In vivo blood clearance experiments showed that 111 In-ICG-DPDCs had a relative long blood circulation time with the fast and slow phase half-lives of 40 and 132.7 min. 111In-ICG-DPDCs accumulated mainly in the liver and spleen, with long retention time. NanoScanSPECT/CT imaging showed that LLC tumors were significantly visualized at 4 h post-injection, and the other major accumulated organs were the liver and spleen, which were consistent with the results of biodistribution. Optical imaging showed significant uptake of the nanoparticle probe in the tumor, confirming the SPECT imaging results. Conclusion The Cerasome based probe designed could be used for tumor SPECT and optical dual-modality imaging, and has potential for therapeutic use.