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化学进展 2020, Vol. 32 Issue (9): 1252-1263 DOI: 10.7536/PC200209 前一篇   后一篇

• 综述 •

基于纳米颗粒的化学发光技术在炎症及肿瘤诊疗中的应用

丁静静1, 黄利利1, 谢海燕1,**   

  1. 1. 北京理工大学生命学院 北京 100081
  • 收稿日期:2020-02-14 修回日期:2020-04-10 出版日期:2020-09-24 发布日期:2020-06-30
  • 通讯作者: 谢海燕
  • 作者简介:
    **Corresponding author e-mail:
  • 基金资助:
    *国家自然科学基金项目(21874011)
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Application of Nanoparticles-Based Chemiluminescence in Diagnosis and Treatment of Inflammation and Tumor

Ding Jingjing1, Lili Huang1, Haiyan Xie1,**   

  1. 1. School of Life Science, Beijing Institute of Technology, Beijing 100081, China
  • Received:2020-02-14 Revised:2020-04-10 Online:2020-09-24 Published:2020-06-30
  • Contact: Haiyan Xie
  • Supported by:
    the Natural Science Foundation of China(21874011)

光学技术在生物医药领域具有至关重要的作用,它不仅使生物活体的检测变得可视化,还可以提高疾病治疗的特异性和灵敏性。但是普通的光学技术具有组织穿透深度低、信噪比低和组织自发光等问题。针对这些问题,研究者开始关注并研究自发光技术,包括化学发光、生物发光、切伦科夫发光。其中,化学发光(Chemiluminescence,CL)是化学物质在进行化学反应过程中产生的一种光辐射现象,具有灵敏度高、无需外部光源激发、打破组织穿透深度限制、提高信噪比的优势,为光学成像与治疗技术的进一步发展提供了新思路。但是由于化学发光物质的疏水性等问题限制了其在生物医药领域的应用。针对这些问题,研究者开始将纳米技术与化学发光技术进行结合,不仅拓展了化学发光的应用范围,还进一步促进了疾病的诊断与治疗。在此基础上,该文首先分析了化学发光的分子机理,其次总结归纳了化学发光在炎症及肿瘤诊疗中的应用,并探讨了在实际应用中遇到的问题以及未来的发展方向。

关键词： 化学发光, 鲁米诺, 过氧化草酸酯, 过氧化氢, 纳米颗粒, 成像, 治疗

Optical technology plays a vital role in the field of biomedicine. It not only enables visualization of physiological or pathological processes at the cellular and subcellular dimensions in living subjects, but also improves the specificity and sensitivity of disease treatment. However, ordinary optical technology faces many challenges, including relatively low tissue penetration depth, low signal-to-noise ratio, and autofluorescence of the tissue. To overcome these problems, many researchers have gradually begun to focus on self-luminous technologies, including chemiluminescence, bioluminescence, and Cherenkov luminescence. Among them, chemiluminescence(CL) is a kind of light radiation phenomenon, which is produced by chemical substances in the process of chemical reactions. It has many advantages, including high sensitivity, no need for external light source excitation, breaking through the limit of tissue penetration depth, and improving the signal-to-noise ratio. These characteristics provide new ideas for the further development of optical imaging and treatment technology. However, due to the hydrophobicity of the chemiluminescent substance and other problems, its application in the field of biomedicine has been limited. To solve these problems, researchers have begun to combine nanotechnology with chemiluminescence technology, which not only expands the application range of chemiluminescence, but also further promotes the diagnosis and treatment of diseases. On this basis, the article first analyzes the molecular mechanism of chemiluminescence, secondly summarizes the application of chemiluminescence in the diagnosis and treatment of inflammation and tumor, and discusses the problems encountered in practical applications and the future development direction.

Contents

1 Introduction

2 The molecular mechanisms of chemiluminescence

2.1 Direct chemiluminescence

2.2 Indirect chemiluminescence

3 Application of nanoparticles-based chemiluminescence in inflammation and tumor diagnosis

3.1 Nanoparticles-based luminol chemiluminescence imaging

3.2 Nanoparticles-based oxalate peroxide chemiluminescence imaging

4 Application of nanoparticles-based chemiluminescence in tumor treatment

4.1 Nanoparticles-based luminol luminescence-induced tumor treatment

4.2 Nanoparticles-based oxalate peroxide luminescence-induced tumor treatment

4.3 Combination of chemiluminescence-induced photodynamic therapy and other tumor therapies

5 Conclusion and outlook

Key words: chemiluminescence, luminol, oxalate peroxide, hydrogen peroxide, nanoparticles, imaging, therapy
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图1 鲁米诺发光分子机理[18~22]
Fig.1 Mechanism for luminol chemiluminescence[18~22]
图2 (a) 过氧化草酸酯形成能量中间体的分子机理[26];(b) 能量中间体激发荧光分子发光的分子机理[27,28]
Fig.2 (a) Formation of 1,2-dioxetanedione[26];(b) Schuster’s CIEEL mechanism on the 1,2-dioxetanedione[27,28]
图3 金纳米颗粒在增强鲁米诺发光强度方面的应用[40]
Fig.3 Application of gold nanoparticles in enhancing luminous intensity[40]
图4 (A) Luminol-R纳米颗粒的发光光谱;(B) Luminol-R纳米颗粒的肿瘤转移灶活体成像[41];(C) DiI-DiD纳米泡的构建及发光机理;(D) DiI-DiD纳米泡肿瘤成像[42]
Fig.4 (A) The spectrum of Luminol-R;(B) The tumor metastases imaging of Luminol-R nanoparticles[41];(C) Construction and luminescence mechanism of DiI-DiD nanobubbles;(D) The tumor imaging of DiI-DiD nanobubble[42]
图5 (a) FPOC纳米颗粒的构建与关节炎活体成像[46];(b) 波长可调纳米颗粒的构建与关节炎活体成像[47]
Fig.5 (a) FPOC NPs and in vivo CL imaging of arthritis in the LPS induction model[46];(b) Construction of wavelength-tunable nanoparticles and in vivo imaging of arthritis[47]
图6 SPN-NIR纳米颗粒的构建与神经性炎症和腹膜炎成像[52]
Fig.6 Construction of SPN-NIR nanoparticles and the imaging of neuroinflammation and peritonitis[52]
图7 (a) CSN纳米颗粒的构建与生物标志物检测机理;(b) G-CSN在胰岛素敏感剂筛选中的应用[53]
Fig.7 (a) Fabrication process of the CSN and its application in intracellular oxidase-catalyzed biomarker detection;(b) Response of G-CSN-labeled cells for insulin sensitizer screening[53]
图8 (a) CLP纳米颗粒的构建与光动力治疗机理;(b) CLP肿瘤抑制效果[64]
Fig.8 (a) Construction of the CLP and the mechanism of photodynamic therapy;(b) Tumor suppressive effect[64]
图9 (a) 鲁米诺-H2O2-HRP体系构建及发光原理;(b) 各物质吸收光谱;(c) 不同条件下ROS生成对比[65]
Fig.9 (a) Schematic representation of the mechanism of ROS generation for PDT and fluorescence imaging upon the addition of chemiluminescence substrates;(b) Normalized absorption spectra of m-THPC and HO-Pdots and emission spectra of HO-Pdots and the chemiluminescence of luminol;(c) Comparison of the absorbance change of ABDA by HO-Pdots with or without m-THPC doped as a function of irradiation time[65]
图10 (a) CL-诱导的 y-CDs-Ce6 PDT系统的构建及ROS产生的机理;(b) 各物质吸收光谱;(c) 活体肿瘤抑制率统计[66]
Fig.10 (a) Construction of the CL-induced y-CDs-Ce6 PDT system and the mechanism of photodynamic therapy;(b) Normalized absorption spectra of y-CDs and Ce6 and emission spectra of y-CDs and the luminol-H2O2-HRP CL system;(c) Tumor inhibition of mice after 20 days of treatments[66]
图11 POCL纳米颗粒的构建及其光动力治疗的机理[68]
Fig.11 Construction of POCL and the principle of singlet oxygen production and the therapeutic effects [68]
图12 化学发光在药物释放方面的应用[69]
Fig.12 The application of chemiluminescence in drug delivery[69]
图13 Hb-NPs@liposome纳米颗粒的构建与光动力与化疗联合治疗的机理[70]
Fig.13 Construction of Hb-NPs@liposome and the mechanism of photodynamic and chemotherapy combined therapy[70]
图14 仿生纳米颗粒的构建和单线态氧产生原理及其在肺转移模型治疗效果[71]
Fig.14 Construction of bionic nanoparticles and the principle of singlet oxygen production and the therapeutic effects in lung metastasis model [71]
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