上海交通大学学报（医学版）

上海交通大学学报（医学版） >

2023 , Vol. 43 >Issue 4: 474 - 479

DOI: https://doi.org/10.3969/j.issn.1674-8115.2023.04.010

综述

恶性肿瘤荧光成像的研究进展

  • 王文博 ,
  • 张方蓉 ,
  • 石亭旺 ,
  • 陈云丰
展开
  • 1.上海交通大学医学院附属第六人民医院骨科，上海 200233
    2.西安电子科技大学广州研究院，广州 510555
王文博（1999—），男，博士生；电子信箱：Wang-wen-bo@sjtu.edu.cn。
陈云丰，电子信箱：chenyf@sjtu.edu.cn。

收稿日期: 2022-09-06

  录用日期: 2023-02-21

  网络出版日期: 2023-04-28

基金资助

国家自然科学基金(82172455);上海交通大学“交大之星”计划医工交叉研究基金(YG2021ZD22);上海市科学技术委员会“科技创新行动计划”生物医药科技支撑专项项目(22S31900200)

收起

Advances in fluorescence imaging of malignant tumors

  • Wenbo WANG ,
  • Fangrong ZHANG ,
  • Tingwang SHI ,
  • Yunfeng CHEN
Expand
  • 1.Department of Orthopaedics, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
    2.Guangzhou Institute of Technology, Xidian University, Guangzhou 510555, China
CHEN Yunfeng, E-mail: chenyf@sjtu.edu.cn.

Received date: 2022-09-06

  Accepted date: 2023-02-21

  Online published: 2023-04-28

Supported by

National Natural Science Foundation of China(82172455);Medical Engineering Cross Project of Shanghai Jiao Tong University(YG2021ZD22);Biomedical Science and Technology Project of Science and Technology Commission of Shanghai Municipality(22S31900200)

Fold

摘要

恶性肿瘤是威胁人类健康的常见疾病，早期诊断并完整切除可显著改善恶性肿瘤患者的预后。目前，临床上用于恶性肿瘤检查的影像学技术多存在灵敏度和时空分辨率差、成像扫描时间长等问题，无法对其行早期诊断，也难以满足手术导航的要求。作为一种具有优异成像特性的新型成像技术，荧光成像能够对生物组织器官的结构和功能进行实时成像，即通过设计高灵敏度、高选择性和特异性的荧光探针，实现对恶性肿瘤的精准检测；其灵敏度主要取决于探针的荧光基团，选择性和特异性则取决于探针是否采取有效的靶向策略。研究显示，发射波长在近红外窗口内的近红外荧光团，尤其在近红外第二窗口内的荧光团，其光学性质优异，可有效提升恶性肿瘤荧光成像的灵敏度；同时，基于恶性肿瘤独特的结构和代谢特性，各种靶向策略也已被开发出来用于设计“常亮”型荧光探针和“激活”型荧光探针，以显著提高恶性肿瘤荧光成像的选择性和特异性。基于此，该文对新近开发的近红外荧光团以及荧光探针靶向恶性肿瘤的策略进行综述。

关键词： 荧光成像; 恶性肿瘤; 近红外荧光团; “常亮”型荧光探针; “激活”型荧光探针

本文引用格式

王文博 , 张方蓉 , 石亭旺 , 陈云丰 . 恶性肿瘤荧光成像的研究进展[J]. 上海交通大学学报（医学版）, 2023 , 43(4) : 474 -479 . DOI: 10.3969/j.issn.1674-8115.2023.04.010

Abstract

Malignant tumors are common diseases that threaten human health. Early diagnosis and complete resection can significantly improve the prognosis of patients with malignant tumors. At present, the imaging techniques used clinically for malignant tumor detection have problems such as poor sensitivity and temporal-spatial resolution, long scanning time, etc., which cannot achieve early diagnosis and meet the requirements of surgical navigation. As a new imaging technology with excellent imaging characteristics, fluorescence imaging can perform real-time imaging of the structure and function of biological tissues and organs. It can realize the accurate detection of malignant tumors by designing fluorescent probes with high sensitivity, high selectivity and specificity. The sensitivity of fluorescence imaging mainly depends on the fluorophore of the probe, and the selectivity and specificity mainly depend on whether the probe adopts an effective targeting strategy. Studies have shown that near infrared fluorophores with emission wavelengths in the near infrared window, especially those in the near infrared Ⅱ window, have excellent optical properties, which can effectively improve the sensitivity of fluorescence imaging of malignant tumors; at the same time, based on the unique structure and metabolic features of malignant tumors, various targeting strategies have been developed to design "always-on" fluorescent probes and "turn-on" fluorescent probes, which significantly improved the selectivity and specificity of fluorescent imaging of malignant tumors. In this paper, the newly developed near infrared fluorophores and the strategies of fluorescent probes targeting malignant tumors are reviewed.

Key words： fluorescence imaging; malignant tumor; near infrared fluorophore; "always on" fluorescent probe; "turn on" fluorescent probe

参考文献

1 SUNG H, FERLAY J, SIEGEL R L, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249.
2 EGLOFF-JURAS C, BEZDETNAYA L, DOLIVET G, et al. NIR fluorescence-guided tumor surgery: new strategies for the use of indocyanine green[J]. Int J Nanomedicine, 2019, 14: 7823-7838.
3 SCHOUW H M, HUISMAN L A, JANSSEN Y F, et al. Targeted optical fluorescence imaging: a meta-narrative review and future perspectives[J]. Eur J Nucl Med Mol Imaging, 2021, 48(13): 4272-4292.
4 WANG S, REN W X, HOU J T, et al. Fluorescence imaging of pathophysiological microenvironments[J]. Chem Soc Rev, 2021, 50(16): 8887-8902.
5 ITO R, KAMIYA M, URANO Y. Molecular probes for fluorescence image-guided cancer surgery[J]. Curr Opin Chem Biol, 2022, 67: 102112.
6 TANG Y F, PEI F, LU X M, et al. Recent advances on activatable NIR-Ⅱ fluorescence probes for biomedical imaging[J]. Adv Optical Mater, 2019, 7(21): 1900917.
7 LI C, GUAN X, ZHANG X, et al. NIR-Ⅱ bioimaging of small molecule fluorophores: from basic research to clinical applications[J]. Biosens Bioelectron, 2022, 216: 114620.
8 LI S J, CHENG D, HE L W, et al. Recent progresses in NIR-Ⅰ/Ⅱfluorescence imaging for surgical navigation[J]. Front Bioeng Biotechnol, 2021, 9: 768698.
9 CHEN Q Y, XIE J W, ZHONG Q, et al. Safety and efficacy of indocyanine green tracer-guided lymph node dissection during laparoscopic radical gastrectomy in patients with gastric cancer: a randomized clinical trial[J]. JAMA Surg, 2020, 155(4): 300-311.
10 HE K S, HONG X P, CHI C W, et al. Efficacy of near-infrared fluorescence-guided hepatectomy for the detection of colorectal liver metastases: a randomized controlled trial[J]. J Am Coll Surg, 2022, 234(2): 130-137.
11 LI D L, LIU Q, QI Q R, et al. Gold nanoclusters for NIR-Ⅱ fluorescence imaging of bones[J]. Small, 2020, 16(43): e2003851.
12 LI D F, HE S Q, WU Y F, et al. Excretable lanthanide nanoparticle for biomedical imaging and surgical navigation in the second near-infrared window[J]. Adv Sci (Weinh), 2019, 6(23): 1902042.
13 ZHOU H, LI S S, ZENG X D, et al. Tumor-homing peptide-based NIR-Ⅱ probes for targeted spontaneous breast tumor imaging[J]. Chin Chem Lett, 2020, 31(6): 1382-1386.
14 KALYANE D, RAVAL N, MAHESHWARI R, et al. Employment of enhanced permeability and retention effect (EPR): nanoparticle-based precision tools for targeting of therapeutic and diagnostic agent in cancer[J]. Mater Sci Eng C Mater Biol Appl, 2019, 98: 1252-1276.
15 JOSHI B P, HARDIE J, FARKAS M E. Harnessing biology to deliver therapeutic and imaging entities via cell-based methods[J]. Chemistry, 2018, 24(35): 8717-8726.
16 ON K C, RHO J, YOON H Y, et al. Tumor-targeting glycol chitosan nanoparticles for image-guided surgery of rabbit orthotopic VX2 lung cancer[J]. Pharmaceutics, 2020, 12(7): 621.
17 XU Y L, WU H, HUANG J, et al. Probing and enhancing ligand-mediated active targeting of tumors using sub-5 nm ultrafine iron oxide nanoparticles[J]. Theranostics, 2020, 10(6): 2479-2494.
18 DE JONGH S J, TJALMA J J J, KOLLER M, et al. Back-table fluorescence-guided imaging for circumferential resection margin evaluation using bevacizumab-800CW in patients with locally advanced rectal cancer[J]. J Nucl Med, 2020, 61(5): 655-661.
19 VOSKUIL F J, DE JONGH S J, HOOGHIEMSTRA W T R, et al. Fluorescence-guided imaging for resection margin evaluation in head and neck cancer patients using cetuximab-800CW: a quantitative dose-escalation study[J]. Theranostics, 2020, 10(9): 3994-4005.
20 MUSELAERS C H J, STILLEBROER A B, RIJPKEMA M, et al. Optical imaging of renal cell carcinoma with anti-carbonic anhydrase Ⅸ monoclonal antibody girentuximab[J]. J Nucl Med, 2014, 55(6): 1035-1040.
21 ZETTLITZ K A, TSAI W T K, KNOWLES S M, et al. Dual-modality immuno-PET and near-infrared fluorescence imaging of pancreatic cancer using an anti-prostate stem cell antigen cys-diabody[J]. J Nucl Med, 2018, 59(9): 1398-1405.
22 BOOGERD L S F, BOONSTRA M C, PREVOO H A J M, et al. Fluorescence-guided tumor detection with a novel anti-EpCAM targeted antibody fragment: preclinical validation[J]. Surg Oncol, 2019, 28: 1-8.
23 AMINI A, SAFDARI Y, TASH SHAMSABADI F. Near-infrared fluorescence imaging of EGFR-overexpressing tumors in the mouse xenograft model using scFv-IRDye800CW and cetuximab-IRDye800CW[J]. Mol Imaging, 2022, 2022: 9589820.
24 DE VALK K S, DEKEN M M, HANDGRAAF H J M, et al. First-in-human assessment of cRGD-ZW800-1, a zwitterionic, integrin-targeted, near-infrared fluorescent peptide in colon carcinoma[J]. Clin Cancer Res, 2020, 26(15): 3990-3998.
25 MO T, LIU X Y, LUO Y Q, et al. Aptamer-based biosensors and application in tumor theranostics[J]. Cancer Sci, 2022, 113(1): 7-16.
26 WANG J, FANG X N, ZHANG C C, et al. Development of aptamer-based molecular tools for rapid intraoperative diagnosis and in vivo imaging of serous ovarian cancer[J]. ACS Appl Mater Interfaces, 2021, 13(14): 16118-16126.
27 ZHU L, ZHONG Y, WU S, et al. Cell membrane camouflaged biomimetic nanoparticles: focusing on tumor theranostics[J]. Mater Today Bio, 2022, 14: 100228.
28 RAO L, HE Z B, MENG Q F, et al. Effective cancer targeting and imaging using macrophage membrane-camouflaged upconversion nanoparticles[J]. J Biomed Mater Res A, 2017, 105(2): 521-530.
29 ZHANG Y, ZHANG G P, ZENG Z L, et al. Activatable molecular probes for fluorescence-guided surgery, endoscopy and tissue biopsy[J]. Chem Soc Rev, 2022, 51(2): 566-593.
30 BOEDTKJER E, PEDERSEN S F. The acidic tumor microenvironment as a driver of cancer[J]. Annu Rev Physiol, 2020, 82: 103-126.
31 ZHAO T, HUANG G, LI Y, et al. A transistor-like pH nanoprobe for tumour detection and image-guided surgery[J]. Nat Biomed Eng, 2016, 1: 0006.
32 WITJES M, VOSKUIL F, STEINKAMP P, et al. Fluorescence guided surgery using the pH-activated micellar tracer ONM-100: first-in-human proof of principle in head and neck squamous cell carcinoma[J]. J Oral Maxillofac Surg, 2019, 77(9): e38.
33 DOU K, HUANG W J, XIANG Y H, et al. Design of activatable NIR-Ⅱ molecular probe for in vivo elucidation of disease-related viscosity variations[J]. Anal Chem, 2020, 92(6): 4177-4181.
34 UNKART J T, CHEN S L, WAPNIR I L, et al. Intraoperative tumor detection using a ratiometric activatable fluorescent peptide: a first-in-human phase 1 study[J]. Ann Surg Oncol, 2017, 24(11): 3167-3173.
35 SMITH B L, LANAHAN C R, SPECHT M C, et al. Feasibility study of a novel protease-activated fluorescent imaging system for real-time, intraoperative detection of residual breast cancer in breast conserving surgery[J]. Ann Surg Oncol, 2020, 27(6): 1854-1861.
36 CAO J, ZHU B L, ZHENG K F, et al. Recent progress in NIR-Ⅱ contrast agent for biological imaging[J]. Front Bioeng Biotechnol, 2020, 7: 487.
Options
文章导航

/

〈 〉