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吲哚菁绿纳米颗粒选择性地被淋巴系统摄取、分布和保留,从而能够详细地描绘淋巴管、淋巴结和异常情况。

Indocyanine green nanoparticles undergo selective lymphatic uptake, distribution and retention and enable detailed mapping of lymph vessels, nodes and abnormalities.

机构信息

a Department of Pharmaceutics , University of Washington , Seattle , WA , USA.

b Department of Comparative Medicine , University of Washington , Seattle , WA , USA.

出版信息

J Drug Target. 2018 Jun-Jul;26(5-6):494-504. doi: 10.1080/1061186X.2018.1433681. Epub 2018 Feb 12.

Abstract

The distributed network of lymph vessels and nodes in the body, with its complex architecture and physiology, presents a major challenge for whole-body lymphatic-targeted drug delivery. To gather physiological and pathological information of the lymphatics, near-infrared (NIR) fluorescence imaging of NIR fluorophores is used in clinical practice due to its tissue-penetrating optical radiation (700-900 nm) that safely provides real-time high-resolution in vivo images. However, indocyanine green (ICG), a common clinical NIR fluorophore, is unstable in aqueous environments and under light exposure, and its poor lymphatic distribution and retention limits its use as a NIR lymphatic tracer. To address this, we investigated in mice the distribution pathways of a novel nanoparticle formulation that stabilises ICG and is optimised for lymphatic drug delivery. From the subcutaneous space, ICG particles provided selective lymphatic uptake, lymph vessel and node retention, and extensive first-pass lymphatic distribution of ICG, enabling 0.2 mm and 5-10 cell resolution of lymph vessels, and high signal-to-background ratios for lymphatic vessel and node networks. Soluble (free) ICG readily dissipated from lymph vessels local to the injection site and absorbed into the blood. These unique characteristics of ICG particles could enable mechanistic studies of the lymphatics and diagnosis of lymphatic abnormalities.

摘要

体内淋巴管和淋巴结的分布式网络具有复杂的结构和生理学特性,这对全身淋巴靶向药物输送构成了重大挑战。为了收集淋巴管的生理和病理信息,近红外(NIR)荧光成像是在临床实践中使用近红外荧光团进行的,因为它具有组织穿透光学辐射(700-900nm),可安全地提供实时高分辨率的体内图像。然而,吲哚菁绿(ICG)作为一种常见的临床近红外荧光团,在水相环境中和光暴露下不稳定,其淋巴管分布和保留不佳限制了其作为近红外淋巴示踪剂的应用。为了解决这个问题,我们在小鼠中研究了一种新型纳米颗粒制剂的分布途径,该制剂稳定 ICG 并优化了用于淋巴药物输送。从皮下空间,ICG 颗粒提供了选择性的淋巴管摄取、淋巴管和淋巴结保留,以及 ICG 的广泛的初次通过淋巴分布,能够分辨 0.2mm 和 5-10 个细胞分辨率的淋巴管,并具有高的淋巴管和淋巴结网络的信号与背景比值。可溶性(游离)ICG 容易从注射部位附近的淋巴管消散,并被吸收到血液中。ICG 颗粒的这些独特特征可以实现对淋巴管的机制研究和对淋巴异常的诊断。

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