177Lu-Labeled Cerasomes Encapsulating Indocyanine Green for Cancer Theranostics
177Lu-Labeled Cerasomes Encapsulating Indocyanine Green for Cancer Theranostics
复制标题
177Lu 标记的陶瓷体封装吲哚菁绿用于癌症治疗诊断
DOI：
10.1021/acsami.5b07856
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发表时间：
2015-10-07
影响因子：
9.5
通讯作者：
Tian, Jie
中科院分区：
文献类型：
--
作者：
Jing, Lijia;Shi, Jiyun;Tian, Jie
本文报道了通过引入1，2-二硬脂酰-sn-甘油基-3-磷酸乙醇-胺-N-[羧基（聚乙二醇）2000]-1，4，7，10-四氮杂环十二烷-1，4，7，10-四乙酸单酰胺（DSPE-PEG（2000）-DOTA），然后螯合放射性同位素Lu-177，制备了一种稳健的包封吲哚菁绿色（ICG）的治疗诊断神经酰胺体。研究了它在肿瘤摄取和生物分布的光学和核成像以及光热杀伤癌细胞方面的应用。结果表明，所制备的神经酰胺酶体可有效地作为荧光造影剂和核成像示踪剂。将ICG包裹到神经酰胺脂质体中，可以有效地防止ICG在体内的降解、聚集和快速消除，从而显著改善ICG的近红外荧光成像、光热稳定性和体内药代动力学特性。荧光和核成像均显示，在将神经酰胺酶体剂静脉注射到荷刘易斯肺癌小鼠中后，该剂可选择性地在肿瘤部位积聚，从而通过在最佳时间窗一次性近红外激光照射实现肿瘤的有效光热消融。在全身基础上追踪神经酰胺脂质体的摄取的能力可以为研究人员开发基于神经酰胺脂质体的药物递送剂提供极好的工具，特别是用治疗诊断放射性核素Lu-177标记神经酰胺脂质体的策略，使Lu-177标记的神经酰胺脂质体能够用于放射性核素癌症治疗甚至联合治疗。
This Article reported the fabrication of a robust theranostic cerasome encapsulating indocyanine green (ICG) by incorporating 1,2-distearoyl-sn-glycero-3-phosphoethanol-amine-N-[carboxy(polyethylene glycol)2000]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid monoamide (DSPE-PEG(2000)-DOTA), followed by chelating radioisotope of Lu-177. Its applications in optical and nuclear imaging of tumor uptake and biodistribution, as well as photothermal killing of cancer cells, were investigated. It was found that the obtained cerasome could act efficiently as fluorescence contrast agent as well as nuclear imaging tracer. Encapsulating ICG into cerasome could protect ICG from degradation, aggregation, and fast elimination from body, resulting in remarkable improvement in near-infrared fluorescence imaging, photothermal stability, and in vivo pharmacokinetic profile. Both fluorescence and nuclear imaging showed that such agent could selectively accumulate in tumor site after intravenous injection of the cerasome agent into Lewis lung carcinoma tumor bearing mice, resulting in efficient photothermal ablation of tumor through a one-time NIR laser irradiation at the best time window. The ability to track the uptake of cerasomes on a whole body basis could provide researchers with an excellent tool for developing cerasome-based drug delivery agents, especially the strategy of labeling cerasomes with theranostic radionuclide Lu-177, enabling the ability of the Lu-177-labeled cerasomes for radionuclide cancer therapy and even the combined therapy.