Evaluation of Temperature-Sensitive, Indocyanine Green-Encapsulating Micelles for Noninvasive Near-Infrared Tumor Imaging
Evaluation of Temperature-Sensitive, Indocyanine Green-Encapsulating Micelles for Noninvasive Near-Infrared Tumor Imaging
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DOI：
10.1007/s11095-010-0190-y
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发表时间：
2010-09-01
影响因子：
3.7
通讯作者：
Pun, Suzie H.
中科院分区：
文献类型：
--
作者：
Kim, Tae Hee;Chen, Yongping;Pun, Suzie H.
目的 吲哚菁绿 (ICG) 是一种 FDA 批准的近红外 (NIR) 染料，具有作为肿瘤检测造影剂的潜在应用。由于 ICG 与血浆蛋白牢固结合，并且表现出水、光和热不稳定性，因此其目前的应用很大程度上仅限于监测血流。为了解决这些问题，将 ICG 封装并稳定在由热敏嵌段共聚物 Pluronic F-127、聚环氧乙烷-聚环氧丙烷-聚环氧乙烷形成的聚合物胶束中，以增加 ICG 的稳定性和循环时间。方法在不同浓度的 Pluronic 和 ICG 下制备负载 ICG 的 Pluronic 胶束，并通过测定粒径、染料负载效率和染料降解动力学进行表征。采用福斯特共振能量转移光谱法监测 Pluronic 胶束在生理溶液中的稳定性。静脉注射给 CT-26 结肠癌荷瘤小鼠后，还测定了负载 ICG 的胶束的血浆清除动力学和生物分布，并进行近红外全身成像以检测肿瘤。结果 Pluronic F-127 胶束表现出高效的 ICG 负载、小尺寸、稳定的 ICG 荧光和延长的体内循环。静脉注射装载 ICG 的胶束后，小鼠体内的实体瘤得到了特别的可视化。结论因此，这些材料是用于非侵入性近红外肿瘤成像应用的有前景的制剂。
Purpose Indocyanine green (ICG), an FDA-approved near infrared (NIR) dye, has potential application as a contrast agent for tumor detection. Because ICG binds strongly to plasma proteins and exhibits aqueous, photo, and thermal instability, its current applications are largely limited to monitoring blood flow. To address these issues, ICG was encapsulated and stabilized within polymeric micelles formed from the thermo-sensitive block copolymer Pluronic F-127, poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide), to increase the stability and circulation time of ICG.Methods ICG-loaded Pluronic micelles were prepared at various concentrations of Pluronic and ICG and characterized by determining particle sizes, dye loading efficiency, and the kinetics of dye degradation. Forster resonance energy transfer spectroscopy was employed to monitor the stability of Pluronic micelles in physiological solutions. The plasma clearance kinetics and biodistribution of ICG-loaded micelles was also determined after intravenous delivery to CT-26 colon carcinoma tumor-bearing mice, and NIR whole-body imaging was performed for tumor detection.Results The Pluronic F-127 micelles showed efficient ICG loading, small size, stabilized ICG fluorescence, and prolonged circulation in vivo. Solid tumors in mice were specifically visualized after intravenous administration of ICG-loaded micelles.Conclusions These materials are therefore promising formulations for noninvasive NIR tumor imaging applications.