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化学进展 2022, Vol. 34 Issue (1): 198-206 DOI: 10.7536/PC201237 前一篇   后一篇

• 综述 •

可激活的NIR-Ⅱ探针用于肿瘤成像

王振1, 李曦2, 栗园园1, 王其1, 卢晓梅2,*(), 范曲立1,*()   

  1. 1 南京邮电大学 信息材料与纳米技术研究院 有机电子与信息显示国家重点实验室 南京 210023
    2 南京工业大学先进材料研究院 南京 211816
  • 收稿日期:2020-12-22 修回日期:2021-01-11 出版日期:2022-01-20 发布日期:2021-03-04
  • 通讯作者: 卢晓梅, 范曲立
  • 基金资助:
    国家自然科学基金项目(21602112)
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Activatable NIR-Ⅱ Probe for Tumor Imaging

Zhen Wang1, Xi Li2, Yuanyuan Li1, Qi Wang1, Xiaomei Lu2(), Quli Fan1()   

  1. 1 State Key Laboratory for Organic Electronics and Information Displays, Institute of Advanced Materials, Nanjing University of Posts & Telecommunications,Nanjing 210023, China
    2 Institute of Advanced Materials, Nanjing Tech University, Nanjing 211816, China
  • Received:2020-12-22 Revised:2021-01-11 Online:2022-01-20 Published:2021-03-04
  • Contact: Xiaomei Lu, Quli Fan
  • Supported by:
    National Natural Science Foundation of China(21602112)

波长位于1000~1700 nm之间的近红外窗口,通常被称为第二近红外(NIR-Ⅱ)窗口,在生物成像方面(荧光成像、光声成像等),该窗口展现出强大的吸引力。相比在可见光(400~700 nm)区域和第一近红外(NIR-Ⅰ,700~900 nm)窗口的传统成像,NIR-Ⅱ生物成像提供了分辨率高和穿透深度深等优点。但是,目前大多数“always-on”探针,并不能实现更高的信噪比。肿瘤微环境响应型智能药物的成像只在肿瘤中触发,可以克服这一局限性。因此,应充分结合肿瘤微环境和NIR-Ⅱ智能响应探针,充分发挥两者的优势,提高肿瘤的精准诊断。本文从不同的病理参数综述了可激活的NIR-Ⅱ荧光探针在生物成像中的最新研究进展,并对这一新兴的领域所面临的机遇和挑战提出看法。

关键词： NIR-Ⅱ, 荧光成像, 光声成像, 可激活

The near-infrared window with a wavelength between 1000 and 1700 nm is usually called the second near-infrared (NIR-Ⅱ) window. In terms of biological imaging (fluorescence imaging, photoacoustic imaging, etc.), this window shows a strong attraction. Compared with traditional imaging in the visible light (400~700 nm) region and the first near-infrared (NIR-Ⅰ 700~900 nm) window, NIR-Ⅱ bioimaging provides the advantages of high resolution and deep penetration depth. However, most current "always-on" probes cannot achieve a higher signal-to-noise ratio. The imaging of tumor microenvironment-responsive smart drugs is only triggered in tumors, which can overcome this limitation. Therefore, the tumor microenvironment and the NIR-Ⅱ intelligent response probe should be fully combined, and the advantages of both will be fully utilized to improve the accurate diagnosis of tumors. This article reviews the latest research progress of activatable NIR-Ⅱ fluorescent probes in bioimaging from different pathological parameters, and presents views on the opportunities and challenges faced by this emerging field.

Contents

1 Introduction

2 Activatable NIR-Ⅱ fluorescent probe

2.1 pH

2.2 Redox

2.3 Enzyme

3 Activatable NIR-Ⅱ photoacoustic imaging

3.1 pH

3.2 Redox

3.3 Exogenous substances

4 Conclusion and outlook

Key words: NIR-Ⅱ, fluorescence imaging, photoacoustic imaging, activatable
()
图1 不同波长光的(a)组织穿透深度,(b)散射和吸收[9]
Fig. 1 (a) Tissue penetration depth; (b) scattering and absorption of light of different wavelengths[9]
图2 (a)pH激活的NIR-Ⅱ荧光探针BTC1070的结构及其pH传感机理;BTC1070在不同pH值下的(b)吸收变化和(c)发射光谱;(d)无创的胃部pH荧光成像[35]
Fig. 2 (a) The structure of pH-activatable NIR-Ⅱ fluorescence probe BTC1070 and its pH-sensing mechanism; (b) Changes in the absorption and (c) the emission spectra of BTC1070 at different pH; (d) In vivo ratiometric noninvasive fluorescence imaging of gastric pH[35]
图3 (a)Hydro-1080和Et-1080的结构和转化;(b)在980 nm激发下,Hydro-1080响应0.01~1.6 μmol/L ·OH的NIR-Ⅱ荧光光谱;(c)10 μmol/L Hydro-1080对各种干扰物质和·OH的响应;(d)1064 nm激发下不同处理方式的小鼠肝脏NIR-Ⅱ荧光成像[36]
Fig.3 (a) The structure and conversion of Hydro-1080 and Et-1080; (b) NIR-Ⅱ fluorescence spectra of Hydro-1080 in response to 0.01~1.6 μmol/L ·OH under 980 nm excitation; (c) Response of 10 μmol/L Hydro-1080 to various interfering species and ·OH; (d) NIR-Ⅱ fluorescence imaging of mouse liver with different processings under excitation at 1064 nm[36]
图4 (a)V&A@Ag2S探针的构建和体内ONOO-检测的示意图;(b)V&A@Ag2S响应的NIR-Ⅱ荧光光谱;(c)注射V@Ag2S、V&A@Ag2S和A@Ag2S后不同时间点的脑血管损伤和健康小鼠的NIR-Ⅱ荧光成像图[41]
Fig. 4 (a) Schematic illustration of the construction of the V&A@Ag2S probe and detection of ONOO- in vivo; (b) NIR-Ⅱ fluorescence spectra of V&A@Ag2S in response to ONOO-; (c) Timespan of NIR-Ⅱ fluorescence in brain vascular injury and healthy mice at different time points after injection of V@Ag2S, V&A@Ag2S, and A@Ag2S[41]
图5 (a)H2S激活的NIR-Ⅱ荧光探针ZX-NIR的结构和传感机制;(b)NaHS处理后,ZX-NIR的荧光光谱变化;(c)注射ZX-NIR后,荷瘤小鼠的肿瘤区域图像[42]
Fig. 5 (a) The structure and sensing mechanism of H2S-activated NIR-Ⅱ fluorescent probe ZX-NIR; (b) the fluorescence spectrum of ZX-NIR after NaHS treatment; (c)Image of the tumor area in tumor-bearing mice after injection of ZX-NIR[42]
图6 (a)BOD-M-β-Gal的β-Gal酶促活化的传感机制;加入β-Gal后BOD-M-β-Gal NIR-Ⅱ(b)吸收和(c)荧光变化图;(d)注射BOD-M-β-Gal或BOD-M-β-Gal+ D-半乳糖的小鼠的时间依赖性NIR-Ⅱ成像[44]
Fig. 6 (a) Proposed sensing mechanism for β-Gal enzymatic activation of BOD-M-β-Gal; (b) Absorption, (c) NIR-Ⅱ fluorescence of BOD-M-β-Gal upon addition of β-Gal in aqueous solution; (d) Time-dependent NIR-Ⅱ imaging of mice injected with BOD-M-β-Gal or BOD-M-β-Gal + D-galactose[44]
图7 (a)NTR活化IR1048-MZ的催化机理;IR1048-MZ响应的(b)吸收和(c)发射光谱;(d)小鼠时间依赖性NIR-Ⅱ成像[50]
Fig. 7 (a) Catalyzed mechanism of IR1048-MZ activated by NTR; (b) Absorption spectra and (c) emission spectra activated by NTR; (d) Time-dependent NIR-Ⅱ imaging of mice[50]
图8 (a)POM的合成和工作机理的示意图;(b)在不同pH值下POM的吸光度;(c)注射后不同时间点肿瘤部位的NIR-Ⅱ PA图像[55]
Fig.8 (a) Illustration of synthesis and working mechanisms of POM; (b) absorbance of POM at different pH; (c) NIR-Ⅱ PA images of the tumor at different post-injection time points[55]
图9 (a)AB-DS@BSA-N3结构;AB@BSA、 AB-DS@BSA和AB-DS@BSA-N3的(b)吸收和(c)发射光谱;(d)AB@BSA和AB-DS@BSA-N3静脉注射前后Hep2荷瘤裸鼠的PA图像[59]
Fig. 9 (a) AB-DS@BSA-N3 structure; (b) absorption and (c) emission spectra of AB@BSA, AB-DS@BSA and AB-DS@BSA-N3; (d) PA images of Hep2 tumor-bearing nude mice before and after intravenous injection of AB@BSA and AB-DS@BSA- N 3 [ 59 ]
图10 (a)可激活的NIR-Ⅱ PA成像SHT的制备;(b)在PBS缓冲液中具有不同H2O2浓度的SHT的吸收光谱;(c)注射SHT后的4T1荷瘤小鼠的代表性PA图像[61]
Fig.10 (a)Preparation of the activatable NIR-Ⅱ PA imaging SHT. (b) UV-vis-NIR absorbance spectra of SHT with different H2O2 concentrations in PBS buffer. (c) Representative PA images of the 4T1-tumor-bearing mice post injection of SHT[61]
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双光子荧光探针研究及其应用*

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摘要

可激活的NIR-Ⅱ探针用于肿瘤成像