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利用自组装两亲性供体-受体近红外二区染料进行肝损伤长期监测和荧光影像引导的肿瘤手术。

Liver injury long-term monitoring and fluorescent image-guided tumor surgery using self-assembly amphiphilic donor-acceptor NIR-II dyes.

机构信息

School of Pharmacy, Nanchang University, 461 Bayi Road, Nanchang, 330006, China; State Key Laboratory of Drug Research, Molecular Imaging Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

University of Chinese Academy of Sciences, Beijing, 100049, China; State Key Laboratory of Drug Research, Molecular Imaging Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

出版信息

Biosens Bioelectron. 2022 Sep 15;212:114371. doi: 10.1016/j.bios.2022.114371. Epub 2022 May 16.

Abstract

Real-time monitoring of liver dysfunction represents a significant unmet demand in clinical and preclinical research. The second near-infrared window (NIR-II, 1000-1700 nm) fluorescent imaging is an attractive method for biomedical imaging and may be a promising approach for liver dysfunction monitoring. Herein, we designed and synthesized a small-molecule NIR-II dye TQT 1009 with an asymmetric donor-acceptor (D-A) core. By introducing four kinds of polyethylene glycol (PEG) with different length and molecular weights (nK, n = 0.5, 2, 5, 10) to TQT1009, the dye was self-assembled into different nanoparticles named as TQP nK with regulated size and controllable circulation lifetime in vivo. In general, TQP nK showed a super high contrast ratio for blood vessels, bones, intestines, lymph, and tumor imaging. The best-selected probe, TQP 10K, exhibited ultralong in vivo circulation time (>96 h) which was suitable for long-term quantitative monitoring of liver and vessel function at a single dose, implying the excellent prospects compared with ICG, which was quickly eliminated in blood within a few minutes. Meanwhile, TQP 10K also achieved NIR-II surgical navigation of tumor in an extended time window (>7 d). Overall, our results demonstrate the self-assembly PEGylated amphiphilic TQP nK provide a new probe design strategy for liver function monitoring and image-guided tumor surgery in a prolonged time window.

摘要

实时监测肝功能是临床和临床前研究中的一个重大未满足需求。近红外二区(NIR-II,1000-1700nm)荧光成像是一种有吸引力的生物医学成像方法,可能是监测肝功能障碍的一种很有前途的方法。在这里,我们设计并合成了一种小分子 NIR-II 染料 TQT 1009,它具有不对称的给体-受体(D-A)核心。通过将四种不同长度和分子量的聚乙二醇(PEG)(nK,n=0.5、2、5、10)引入 TQT1009,该染料自组装成不同的纳米粒子,命名为 TQP nK,其具有可调节的尺寸和可控制的体内循环寿命。一般来说,TQP nK 对血管、骨骼、肠道、淋巴和肿瘤成像具有超高的对比度。最佳选择的探针 TQP 10K 表现出超长的体内循环时间(>96h),适用于单次剂量下肝脏和血管功能的长期定量监测,与 ICG 相比具有优异的前景,ICG 在几分钟内就会在血液中迅速消除。同时,TQP 10K 还实现了肿瘤的 NIR-II 手术导航,时间窗口延长(>7d)。总之,我们的结果表明,自组装的 PEG 两亲性 TQP nK 为延长时间窗口内的肝功能监测和图像引导肿瘤手术提供了一种新的探针设计策略。

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