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高效荧光和磁性多模态探针,用于肿瘤的长期监测和深层穿透成像。

High-efficiency fluorescent and magnetic multimodal probe for long-term monitoring and deep penetration imaging of tumors.

机构信息

State Key Laboratory of Supramolecular Structure and Materials, Jilin University, Changchun, 130012, China.

Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China and The University of Chinese Academy of Sciences, Beijing, 100049, China.

出版信息

J Mater Chem B. 2019 Sep 11;7(35):5345-5351. doi: 10.1039/c9tb00638a.

Abstract

High-quality multimodal imaging requires exogenous contrast agents with high sensitivity, spatial-temporal resolution, and high penetration depth for the accurate diagnosis and surveillance of cancer. Herein, we design a highly efficient fluorescent and magnetic multimodal probe by doping fluorescent molecule 2-(4-bromophenyl)-3-(4-(4-(diphenylamino)styryl)phenyl)fumaronitrile (TB) with near-infrared (NIR) fluorescent emission (714 nm) and superparamagnetic iron oxide (SPIO) into a polystyrene-polyethylene glycol (PS-PEG) matrix to form TB/SPIO@PS-PEG nanoparticles (TSP NPs). The as-prepared TSP NPs exhibit red aggregation-induced emission (AIE) with a maximum wavelength at 655 nm and high fluorescence quantum yield (QY) of 14.6%, facilitating the improvement of sensitivity and signal-to-background ratio for fluorescence molecular imaging (FMI). Phase behavior investigation of the TB/SPIO@PS-PEG probe system by Flory-Huggins lattice theory elucidates the highly efficient fluorescence of the multimodal probe, originating from the poor miscibility between TB and SPIO. Meanwhile, the TSP NPs possess good superparamagnetism and relaxivity and can thus be used as appropriate magnetic contrast agents for magnetic resonance imaging (MRI) and magnetic particle imaging (MPI). In addition, the good biocompatibility and photostability of the TSP NPs make them suitable for long-term monitoring. In vivo fluorescence imaging results indicate that the TSP NPs can facilitate monitoring of subcutaneous tumor growth for more than 24 days in a real-time manner. Multimodal imaging consisting of FMI, MRI, and MPI reveals that TSP NPs can monitor a liver tumor in situ with almost unlimited depth in tissues and high temporal-spatial resolution. As a multimodal probe, the TSP NPs manifest obvious synergistic advantages of long-term monitoring and high penetration depth and hold great prospects in tumor imaging.

摘要

高质量的多模态成像是准确诊断和监测癌症所必需的,需要具有高灵敏度、时空分辨率和高穿透深度的外源性对比剂。在此,我们通过将具有近红外(NIR)荧光发射(714nm)和超顺磁性氧化铁(SPIO)的荧光分子 2-(4-溴苯基)-3-(4-(4-(二苯氨基)乙烯基)苯基)丁二腈(TB)掺杂到聚苯乙烯-聚乙二醇(PS-PEG)基质中,设计了一种高效的荧光和磁共振双模探针,形成 TB/SPIO@PS-PEG 纳米粒子(TSP NPs)。所制备的 TSP NPs 表现出红色聚集诱导发射(AIE),最大波长为 655nm,荧光量子产率(QY)高达 14.6%,有助于提高荧光分子成像(FMI)的灵敏度和信号背景比。通过 Flory-Huggins 格子理论对 TB/SPIO@PS-PEG 探针体系的相行为进行研究,阐明了多模态探针的高效荧光,这源于 TB 和 SPIO 之间较差的混溶性。同时,TSP NPs 具有良好的超顺磁性和弛豫率,因此可用作磁共振成像(MRI)和磁性粒子成像(MPI)的合适磁共振对比剂。此外,TSP NPs 具有良好的生物相容性和光稳定性,使其适用于长期监测。体内荧光成像结果表明,TSP NPs 可实时监测皮下肿瘤生长超过 24 天。由 FMI、MRI 和 MPI 组成的多模态成像显示,TSP NPs 可原位监测组织内几乎无限深度的肝肿瘤,具有高时空分辨率。作为一种多模态探针,TSP NPs 表现出长期监测和高穿透深度的明显协同优势,在肿瘤成像方面具有广阔的前景。

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