近红外荧光手术导航探针的研究进展

doi:10.6023/cjoc202401019

摘要/Abstract

近红外荧光(near-infrared fluorescence, NIRF)成像技术已被证明是外科手术中定位肿瘤部位、识别肿瘤边界以及区分肿瘤细胞和正常组织的有效方法. 开发高质量的NIRF探针对于肿瘤的完全减灭至关重要. 然而, 传统荧光探针在癌组织和健康组织中都能产生荧光信号并且无癌症靶向性, 这导致了相对较高的背景信号和较差的特异性. 近年来, 人们通过纳米修饰、偶联肿瘤靶向配体以及生物标志物激活等方式, 逐渐开发出了更具临床转化价值的荧光探针. 此外, 近红外二区(NIR-II)荧光探针也逐渐成为研究热点. 本文聚焦在荧光手术导航用荧光探针的结构与性能上, 同时对被动靶向型、主动靶向型、可激活型荧光探针以及NIR-II荧光探针进行了全面阐述, 分析其面临的挑战, 探讨可能的解决思路, 以期推动近红外荧光手术导航技术的临床应用.

关键词: 近红外荧光成像, 荧光手术导航, 荧光探针

Near-infrared fluorescence (NIRF) imaging technology has been proved to be an effective method for locating tumor sites, identifying tumor boundaries, and distinguishing tumor cells from normal tissues in surgery. The development of high-quality NIRF probes is crucial for the complete elimination of tumors. However, traditional fluorescent probes can produce fluorescence signals in both cancer tissues and healthy tissues and have no cancer targeting, which lead to relatively high background signals and poor specificity. People have gradually developed fluorescent probes with more clinical transformation value through nano-modification, coupling tumor targeting ligands and biomarker activation, etc. In addition, near-infrared (NIR-II) fluorescent probes have gradually become a research hotspot. This review focuses on the structure and properties of fluorescent probes for fluorescence-based surgical navigation. At the same time, passive targeting, active targeting, activating fluorescent probes and NIR-II fluorescent probes are comprehensively described, and the challenges are analyzed. Possible solutions are discussed in order to promote the clinical application of near-infrared fluorescence-based surgical navigation technology.

Key words: near-infrared fluorescence imaging, fluorescence surgery navigation, fluorescent probe

引用此文

张文艳, 王丹, 罗仁洁, 刘会玲. 近红外荧光手术导航探针的研究进展[J]. 有机化学, 2024, 44(6): 1760-1776.

Wenyan Zhang, Dan Wang, Renjie Luo, Huiling Liu. Research Progress of Near-Infrared Fluorescent Surgical Navigation Probes[J]. Chinese Journal of Organic Chemistry, 2024, 44(6): 1760-1776.

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图/表 24

图1. 菁染料的分子结构

Figure 1. Molecular structure of cyanine dye

图2. ICG (a)和IRDyeCW800 (b)的分子结构

Figure 2. Molecular structures of ICG (a) and IRDyeCW800 (b)

图3. 染料1和2的分子结构

Figure 3. Molecular structures of dyes 1 and 2

图4. 吲哚菁绿(ICG)包覆聚己内酯(PCL)形成胶束示意图

Figure 4. Schematic diagram of indocyanine green (ICG)- coated polycaprolactone (PCL) micelles

图式1. IRDye800CW染料偶联抗体示意图

Scheme 1. Coupling schematic diagram of IRDye800CW dye and antibody

图5. 染料3和4的分子结构

Figure 5. Molecular structures of dyes 3 and 4

图式2. Probe 1 合成示意图

Scheme 2. Schematic diagram of the synthesis of Probe 1

图6. 染料5和6的分子结构

Figure 6. Molecular structures of dyes 5 and 6

图7. EC-17 (a)、OTL38 (b)、染料S0456 (c)和OTL78 (d)的分子结构

Figure 7. Molecular structures of EC-17 (a), OTL38 (b), dye S0456 (c) and OTL78 (d)

图式3. Probe 2 响应示意图

Scheme 3. Probe 2 response diagram

图8. (A)静脉注射Probe 2 (20 mg/kg)后不同时间点皮下肿瘤小鼠模型的荧光成像和(B)近红外成像引导手术过程[99]

Figure 8. (A) After intravenous injection of Probe 2 (20 mg/kg), fluorescence imaging performed on the subcutaneous tumor mouse model at different time points and (B) the procedure of NIR imaging-guided surgery[99]

图式4. Probe 3 响应示意图

Scheme 4. Probe 3 response diagram

图9. (A) A549荷瘤小鼠肿瘤注射Probe 3 (100 μmol/L和25 μL)后不同时间(0、10、20、30、60 min)的代表性荧光图像、 (B)肿瘤的NIRF强度及(C)荷瘤小鼠手术示意图[104]

Figure 9. (A) Representative fluorescence images of A549 tumor-bearing mice at different time points (0, 10, 20, 30, 60 min) after tumor injection of Probe 3 (100 μmol/L and 25 μL), (B) NIRF intensity of tumor, and (C) surgical sketch of tumor-bearing mice[104]

图式5. (a)传统酶可激活型探针响应过程和(b)通过自消除基团释放荧光团过程

Scheme 5. (a) Traditional enzyme-activated probe response process and (b) release fluorophore process by self-eliminating group

图式6. Probe 4 响应示意图

Scheme 6. Probe 4 response diagram

图式7. Probe 5和Probe 6响应示意图

Scheme 7. Probe 5 and Probe 6 response diagram

图式8. Probe 7响应示意图

Scheme 8. Probe 7 response diagram

图10. Probe 8~Probe 13分子结构

Figure 10. Molecular structures of Probe 8~Probe 13

图式9. Probe 13响应示意图

Scheme 9. Probe 13 response diagram

图式10. Probe 14 响应示意图

Scheme 10. Probe 14 response diagram

图11. IR-26 (a)、IR-1061 (b)和FD 1080 (c)的分子结构

Figure 11. Molecular structures of IR-26 (a), IR-1061 (b) and FD 1080 (c)

图12. Probe 15~Probe 17分子结构

Figure 12. Molecular structures of Probe 15~Probe 17

图13. Probe 18 分子结构

Figure 13. Molecular structure of Probe 18

图14. 近红外荧光和SPECT/CT图像

Figure 14. Near-infrared fluorescence and SPECT/CT images (a) In the mouse model of breast cancer subcutaneous tumor, fluorescence imaging was performed on mice after intravenous injection of 100 μg 111In-labeled Probe 18 without trastuzumab blocker (left) and Probe 18 with 1/25 trastuzumab blocker for 72 h (right). (b) SPECT/CT images of mice after intravenous injection of 100 μg 111In-labeled Probe 18 without trastuzumab blocker (left) and Probe 18 with 1/25 trastuzumab blocker for 72 h (right)[150]

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