Nanoprobes for Visualization of Cancer Pathology in Vivo※

doi:10.6023/A21120609

Acta Chimica Sinica ›› 2022, Vol. 80 ›› Issue (6): 805-816.DOI: 10.6023/A21120609 Previous Articles Next Articles

Special Issue: 中国科学院青年创新促进会合辑

Review

肿瘤病理可视化纳米探针的研究进展^※

张沛森^*(), 荆莉红^*()

中国科学院化学研究所胶体、界面与化学热力学院重点实验室北京 100190

投稿日期:2021-12-31 发布日期:2022-07-07
通讯作者: 张沛森, 荆莉红

作者简介:

张沛森, 北京化工大学研究助理, 于2020年在中科院化学研究所获得博士学位. 主要从事纳米生物材料在恶性肿瘤及心脑血管等重大疾病的分子影像学诊断及联合治疗. 主持国家自然科学基金青年项目1项. 以第一/通讯作者在Angew. Chem. Int. Ed., Adv. Mater., Nano Today, Small, Adv. Health. Mater., J. Mater. Chem. B等国际期刊发表SCI论文14篇, 累计发表SCI论文20多篇. 2019年荣获博士研究生国家奖学金, 中科院化学所青年科学奖特别优秀奖.

荆莉红, 博士, 中国科学院青年创新促进会会员, 2011年于中国科学院化学研究所获得理学博士学位, 同年留所工作至今, 期间先后前往香港城市大学及美国麻省理工学院开展研究工作. 主要研究方向包括: (1)量子点光电功能纳米材料的设计合成及性质; (2)肿瘤等恶性生物学事件相关纳米影像探针的构建; (3)重大传染病相关医疗大数据管理及高通量生物信息分析. 截止目前, 主持国家级项目4项、省部级项目3项, 在Sci. Transl. Med., J. Am. Chem. Soc., Adv. Mater., ACS Nano, Nano Today, Chem. Rev., Biomaterials等重要刊物上发表学术论文50多篇.

^※ 庆祝中国科学院青年创新促进会十年华诞.

基金资助:
中国科学院青年创新促进会(2018042); 国家重点研发计划项目(2018YFA0208800); 国家自然科学基金(22177115); 国家自然科学基金(81720108024); 国家自然科学基金(82102679)

Nanoprobes for Visualization of Cancer Pathology in Vivo^※

Peisen Zhang(), Lihong Jing()

Department Key Laboratory of Colloid Interface and Chemical Thermodynamics, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190

Received:2021-12-31 Published:2022-07-07
Contact: Peisen Zhang, Lihong Jing
About author:
^※ Dedicated to the 10th anniversary of the Youth Innovation Promotion Association, CAS.
Supported by:
Youth Innovation Promotion Association CAS(2018042); National Key Research and Development Program of China(2018YFA0208800); National Natural Science Foundation of China(22177115); National Natural Science Foundation of China(81720108024); National Natural Science Foundation of China(82102679)

Cancer progression is often accompanied by a series of complicated variations of molecular pathology, varying enormously between individuals. Therefore, it is necessary to achieve precise diagnosis of tumor, especially at the molecular pathology level. In clinical trials, the traditional medical imaging can identify the position and the anatomical structure of tumors, but it is difficult to reveal their molecular pathology. Although the molecular details of tumors can be obtained later through the pathological analysis of biopsies, this approach is invasive and has spatiotemporal limitations. Unlike these strategies, the pathological biomarkers of tumors can be directly imaged in vivo through the probe-based molecular imaging technology, which aims to quantitatively study the real-time tumorous pathological features at a molecular level. This technology holds huge potentials in the clinical application of precise tumor diagnosis. In recent years, nanomaterials that possess superior optical or magnetic physicochemical properties have become one of the important signal carriers for constructing highly sensitive molecular imaging probes. In this review, the development of nanoprobe-based molecular imaging and the in vivo visualization of tumor molecular pathology are summarized. Specifically, the construction of the pathology responsive nanoprobes is highlighted. The current challenges and perspectives on the future steps needed to implement this nanotechnology in a clinical setting are also discussed.

Key words: pathology, tumor, nanoprobe, molecular imaging, visualization

Cite this article

Peisen Zhang, Lihong Jing. Nanoprobes for Visualization of Cancer Pathology in Vivo^※[J]. Acta Chimica Sinica, 2022, 80(6): 805-816.

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Fig. & Tab. 5

Figure 1. (a) Schematic illustration of the folate receptor (FR)-targeting NaErF4@NaYbF4@NaYF4 nanoprobe; (b) up-conversion (top) and down-conversion (bottom) luminescence images of intraperitoneal tumors in vivo recorded at different time points post-injection of nanoprobe, together with microscopic images of adjacent slices of intraperitoneal tumor extracted (c) upon H&E staining or immunohistochemical staining through anti-vimentin antibody and anti-FR, respectively. The resolution of up-/down-conversion luminescence imaging can be compared through the line spectra drown across the tumorous regions in vivo (right). The scale bars in frame (b) and (c) correspond to 3 mm and 500 µm, respectively[39]

Figure 2. (a) The most possible binding situation between Ir-BTPHSA and β-CD by connection with hydrogen bond; (b) the ROESY spectra of Ir-BTPHSA/CD-NH2; (c) luminescence spectra of Ir-BTPHSA/CD-Cy7 recorded under various oxygen levels upon excitation at 488 nm and 747 nm for Ir-BTPHSA complex and Cy7, respectively (inset: PL intensities of Ir-BTPHSA and Cy7 against oxygen levels); (d) liner fitting of I0'/I' against the oxygen level (I0' and I' refer to PL intensities of Ir-BTPHSA recorded at 0% oxygen and specific oxygen levels, respectively, after normalized with reference PL intensity of Cy7) (inset: normalized PL intensity of Ir-BTPHSA against the oxygen level); (e) quantitative oxygen level mapping of the tumor and its control site[56]

Figure 3. (a) Schematic illustration of the dual-ratiometric fluorescent nanoprobe; (b) quantified pH and MMP-9 expression mapping of tumors obtained at D+0, D+2, and D+4 (in color bar shading from black to yellow for reading MMP-9 expression ranging from of 4.3 to 6.8 ng/mL, each step thus corresponds to 0.25 units), together with the photographs of tumor-bearing mice for 5 d; (c) microscopic image of a tissue slide stained with H&E and merged immunofluorescence microscopic image of two adjacent slides stained for E-cadherin expression (red) and MMP-9 expression (green), respectively (scale bar corresponds to 200 μm). The orange arrows indicate the boundaries between healthy tissue and the tumor where MMP-9 is highly expressed[58]

Figure 4. (a) Illustration to demonstrate the activatable function of UCNP@GA-Fe(III) probe for MRI and its therapeutic function involving multiple pathways; (b) T1-weighted MR images of tumor-bearing mice acquired at different time points pre- and post-injection of nanoprobe; (c) mapping of Fe3+ release based on I475/I800 ratio of upconversion luminescence; (d) the ratio of the integrated signal intensities through above channels for showing Fe3+ release at tumor site against time[70]

Figure 5. (a) Schematic drawings to show molecular mechanism of the GSH-induced agglomeration of the responsive nanoprobes; (b) T1-weighted and (c) T2-weighted MR images of mice bearing orthotopic glioblastoma xenografts acquired before and at different time points after the intravenous injections of nanoprobes; (d) glutathione reductase (GR) and Ki 67 staining of adjacent tumor tissue slices; (e) quantitative mapping of GSH according to imaging data acquired at 7 h post-injection through the correlation between ΔR2/ΔR1 and GSH concentration in vivo[78]

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肿瘤病理可视化纳米探针的研究进展^※

Nanoprobes for Visualization of Cancer Pathology in Vivo^※

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肿瘤病理可视化纳米探针的研究进展※

Nanoprobes for Visualization of Cancer Pathology in Vivo※

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Knowledge

Abstract

Cite this article

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Fig. & Tab. 5

References 84

Related Articles 15

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肿瘤病理可视化纳米探针的研究进展^※

Nanoprobes for Visualization of Cancer Pathology in Vivo^※