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用于近红外二区荧光成像引导下肿瘤及胃肠道梗阻手术治疗的IR820-白蛋白复合物的合理合成

Rational synthesis of IR820-albumin complex for NIR-II fluorescence imaging-guided surgical treatment of tumors and gastrointestinal obstruction.

作者信息

Feng Xinyu, Cao Yuan, Zhuang Pengrui, Cheng Ran, Zhang Xuejun, Liu Hong, Wang Guohe, Sun Shao-Kai

机构信息

School of Medical Imaging, Tianjin Medical University Tianjin 300203 China

Department of Radiology, The Second Hospital of Tianjin Medical University Tianjin 300211 China.

出版信息

RSC Adv. 2022 Apr 21;12(19):12136-12144. doi: 10.1039/d2ra00449f. eCollection 2022 Apr 13.

Abstract

IR820, an analog of FDA-approved indocyanine green, is a promising second near-infrared window (NIR-II) fluorescence probe with better NIR-II fluorescence stability and great clinical transformation potential. Moreover, its fluorescence can be further remarkably enhanced by the interaction with albumin. Therefore, it is significant to flexibly design IR820-albumin complex using endogenous or exogenetic albumin to meet the requirements of different biological applications. Herein, we show the rational synthesis of IR820-albumin complex for NIR-II fluorescence imaging-guided surgical treatment of tumors and gastrointestinal obstruction. We compared the NIR-II fluorescence imaging ability of IR820 pre-incubated with albumin or not to visualize tumors and the gastrointestinal tract and found that the formation of IR820-albumin was essential for the intense NIR-II fluorescence. For imaging-guided tumor treatment, after intravenous injection of free IR820, IR820-albumin complex can be formed due to the presence of plenty of albumin in the blood. For imaging-guided gastrointestinal obstruction removal, IR820-albumin complex should be synthesized before oral administration. NIR-II fluorescence imaging-guided surgeries were successfully realized in both tumor resection and gastrointestinal obstruction removal. Besides, toxicity assessments and confirmed the good biocompatibility of IR820. Our study provides a flexible paradigm for IR820-based NIR-II fluorescence imaging and surgical navigation towards different diseases.

摘要

IR820是美国食品药品监督管理局(FDA)批准的吲哚菁绿的类似物,是一种很有前景的第二近红外窗口(NIR-II)荧光探针,具有更好的NIR-II荧光稳定性和巨大的临床转化潜力。此外,其荧光可通过与白蛋白相互作用而进一步显著增强。因此,灵活设计IR820-白蛋白复合物,利用内源性或外源性白蛋白来满足不同生物应用的需求具有重要意义。在此,我们展示了用于NIR-II荧光成像引导肿瘤手术治疗和胃肠道梗阻治疗的IR820-白蛋白复合物的合理合成。我们比较了预先与白蛋白孵育或未孵育的IR820对肿瘤和胃肠道进行NIR-II荧光成像的能力,发现IR820-白蛋白的形成对于强烈的NIR-II荧光至关重要。对于成像引导的肿瘤治疗,静脉注射游离IR820后,由于血液中存在大量白蛋白,可形成IR820-白蛋白复合物。对于成像引导的胃肠道梗阻解除,应在口服前合成IR820-白蛋白复合物。在肿瘤切除和胃肠道梗阻解除手术中均成功实现了NIR-II荧光成像引导手术。此外,毒性评估证实了IR820具有良好的生物相容性。我们的研究为基于IR820的NIR-II荧光成像以及针对不同疾病的手术导航提供了一种灵活的范例。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f2b/9023119/7fa54adf9484/d2ra00449f-s1.jpg

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