Aminopeptidase N Activatable Nanoprobe for Tracking Lymphatic Metastasis and Guiding Tumor Resection Surgery via Optoacoustic/NIR-II Fluorescence Dual-Mode Imaging
Abstract
Lymphatic metastasis is a crucial mechanism by which the cancer cells break away from the primary (original) tumor and travel to the closest regional lymph node(s) and ultimately to other organs or parts of the body, which is closely associated with tumor recurrence and reduced survival. Thus, tracking tumor lymphatic metastasis and realizing imaging-guided lymphoma resection surgery is of great significance. In this study, an activatable nanoprobe is developed for precisely tracking lymphatic metastasis of tumors and imaging-guided resection of the primary tumor and metastatic lymphoma. The molecular probe contains tricyanofuran as the electron-accepting unit (electron acceptor), xanthene as the electron-donating unit (electron donor), and alanine as the responsive unit (recognition moiety) for aminopeptidase N, and the probe molecules form the nanoprobe with bovine serum albumin as the matrix. The nanoprobe can respond specifically to aminopeptidase N overproduced in the tumor, thereby transmuting the alanine into an amino group, and correspondingly the nanoprobe is activated. Strong optoacoustic and NIR-II fluorescence signals emitted by the activated nanoprobe can be utilized for visualizing the lymphatic metastasis of tumors. Moreover, the nanoprobe with the aid of three-dimensional multispectral optoacoustic tomography (3D MSOT) imaging can accurately locate the tumor site of lymphatic metastasis, and ultimately, both the primary tumor and the metastatic lymphoma can be excised with resection surgery under the guidance of NIR-II fluorescence imaging.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Wu et al. pioneered the development of an aminopeptidase N (APN)-activated PA/NIR-II fluorescence dual-modal imaging probe (TX-APN).
“Wu et al. pioneered the development of an aminopeptidase N (APN)-activated PA/NIR-II fluorescence dual-modal imaging probe (TX-APN) (Fig. 19c)223.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [223]
TX-APN@BSA could be specifically activated by APN, generating strong fluorescent and PA signals at 922 nm and 795 nm, respectively.
“This nanoprobe could be specifically activated by APN, generating strong fluorescent and PA signals at 922 nm and 795 nm, respectively.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [223]
Cites
Near-infrared fluorophores for biomedical imaging
Hong, G., Antaris, A. L., & Dai, H. (2017) · Nature Biomedical Engineering · doi:10.1038/s41551-016-0010 · Cited by 3,013 · see citing works
A small-molecule dye for NIR-II imaging
Antaris, A. L., Chen, H., Cheng, K., Sun, Y., Hong, G., Qu, C., Diao, S., Deng, Z., Hu, X., Zhang, B., et al. (2016) · Nature Materials · doi:10.1038/nmat4476 · Cited by 1,778 · see citing works
Molecular Imaging by Means of Multispectral Optoacoustic Tomography (MSOT)
Ntziachristos, V., & Razansky, D. (2010) · Chemical Reviews · doi:10.1021/cr9002566 · Cited by 778 · see citing works
Mechanisms and Consequences of Alternative Polyadenylation
Di Giammartino, D. C., Nishida, K., & Manley, J. L. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.08.017 · Cited by 737 · see citing works
Liu, Y., Li, Y., Koo, S., Sun, Y., Liu, Y., Liu, X., Pan, Y., Zhang, Z., Du, M., Lu, S., et al. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.1c00553 · Cited by 544 · see citing works
LNMAT1 promotes lymphatic metastasis of bladder cancer via CCL2 dependent macrophage recruitment
Chen, C., He, W., Huang, J., Wang, B., Li, H., Cai, Q., Su, F., Bi, J., Liu, H., Zhang, B., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-06152-x · Cited by 450 · see citing works
A metastasis map of human cancer cell lines
Jin, X., Demere, Z., Nair, K., Ali, A., Ferraro, G. B., Natoli, T. E., Deik, A., Petronio, L., Tang, A. A., Zhu, C., et al. (2020) · Nature · doi:10.1038/s41586-020-2969-2 · Cited by 431 · see citing works
Aminopeptidase N (CD13) as a target for cancer chemotherapy
Wickström, M., Larsson, R. L., Nygren, P., et al. (2010) · Cancer Science · doi:10.1111/j.1349-7006.2010.01826.x · Cited by 359 · see citing works
Li, H., Yao, Q., Sun, W. C., Shao, K., Yang, L. G., Chung, J., Kim, D., Fan, J., Long, S., Du, J., et al. (2020) · Journal of the American Chemical Society · doi:10.1021/jacs.0c01365 · Cited by 305 · see citing works
Multiplexed NIR‐II Probes for Lymph Node‐Invaded Cancer Detection and Imaging‐Guided Surgery
Tian, R., Ma, H., Zhu, S., Lau, J., Ma, R., Liu, Y., Lin, L., Chandra, S., Wang, S., Zhu, X., et al. (2020) · Advanced Materials · doi:10.1002/adma.201907365 · Cited by 269 · see citing works
Albumin-chaperoned cyanine dye yields superbright NIR-II fluorophore with enhanced pharmacokinetics
Tian, R., Zeng, Q., Zhu, S., Lau, J., Chandra, S., Ertsey, R. D., Hettie, K. S., Teraphongphom, N. T., Hu, Z., Niu, G., et al. (2019) · Science Advances · doi:10.1126/sciadv.aaw0672 · Cited by 268 · see citing works
Chemical Design of Activatable Photoacoustic Probes for Precise Biomedical Applications
Liu, Y., Teng, L., Yin, B., Meng, H., Yin, X., Huan, S., Song, G., & Zhang, X. (2022) · Chemical Reviews · doi:10.1021/acs.chemrev.1c00875 · Cited by 249 · see citing works
Lyu, Y., & Pu, K. (2017) · Advanced Science · doi:10.1002/advs.201600481 · Cited by 246 · see citing works
Qi, Y., Huang, Y. X., Li, B., Zeng, F., & Wu, S. (2017) · Analytical Chemistry · doi:10.1021/acs.analchem.7b04407 · Cited by 236 · see citing works
Self-citationDinuclear metal complexes: multifunctional properties and applications
Li, G., Zhu, D., Wang, X., Su, Z., & Bryce, M. R. (2020) · Chemical Society Reviews · doi:10.1039/c8cs00660a · Cited by 228 · see citing works
A bioreducible N-oxide-based probe for photoacoustic imaging of hypoxia
Knox, H. J., Hedhli, J., Kim, T. W., Khalili, K., Dobrucki, L. W., & Chan, J. (2017) · Nature Communications · doi:10.1038/s41467-017-01951-0 · Cited by 222 · see citing works
Shan, L., Zhang, J., Blum, N. T., Li, M., Zhang, D., Yin, W., Zhao, F., Lin, J., & Huang, P. (2022) · Nature Communications · doi:10.1038/s41467-022-29082-1 · Cited by 220 · see citing works
Ouyang, J., Sun, L., Zeng, Z., Zeng, C., Zeng, F., & Wu, S. (2019) · Angewandte Chemie International Edition · doi:10.1002/anie.201913149 · Cited by 212 · see citing works
Self-citationLucero, M. Y., & Chan, J. (2021) · Nature Chemistry · doi:10.1038/s41557-021-00804-0 · Cited by 201 · see citing works
Zhang, X., Chen, Y., He, H., Wang, S., Lei, Z., & Zhang, F. (2021) · Angewandte Chemie International Edition · doi:10.1002/anie.202109728 · Cited by 176 · see citing works
De Novo Design of a Tumor-Penetrating Peptide
Alberici, L., Roth, L., Sugahara, K. N., Agemy, L., Kotamraju, V. R., Teesalu, T., Bordignon, C., Traversari, C., Rizzardi, G., & Ruoslahti, E. I. (2012) · Cancer Research · doi:10.1158/0008-5472.can-12-1668 · Cited by 175 · see citing works
Wu, Y., Huang, S., Wang, J., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-06499-1 · Cited by 163 · see citing works
Chen, R., Huang, S., Lin, T., Ma, H., Shan, W., Duan, F., Lv, J., Zhang, J., Ren, L., & Nie, L. (2021) · Nature Nanotechnology · doi:10.1038/s41565-020-00844-6 · Cited by 152 · see citing works
Hao, X., Li, C., Zhang, Y., Wang, H., Chen, G., Wang, M., & Wang, Q. (2018) · Advanced Materials · doi:10.1002/adma.201804437 · Cited by 143 · see citing works
Chen, J., Chen, L., Wu, Y., Fang, Y., Zeng, F., Wu, S., & Zhao, Y. (2021) · Nature Communications · doi:10.1038/s41467-021-27233-4 · Cited by 140 · see citing works
Self-citationLi, H., Li, Y., Yao, Q., Fan, J., Sun, W. C., Long, S., Shao, K., Du, J., Wang, J., & Peng, X. (2018) · Chemical Science · doi:10.1039/c8sc04685a · Cited by 126 · see citing works
A Renal‐Clearable Macromolecular Reporter for Near‐Infrared Fluorescence Imaging of Bladder Cancer
Huang, J., Jiang, Y., Li, J., He, S., Huang, J., & Pu, K. (2019) · Angewandte Chemie International Edition · doi:10.1002/anie.201911859 · Cited by 125 · see citing works
Design of Aminopeptidase N Inhibitors as Anti-cancer Agents
Amin, S. A., Adhikari, N., & Jha, T. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b00782 · Cited by 124 · see citing works
Gardner, S. H., Brady, C. J., Keeton, C., et al. (2021) · Angewandte Chemie International Edition · doi:10.1002/anie.202105905 · Cited by 119 · see citing works
Clinical Significance of Aminopeptidase N in Non–Small Cell Lung Cancer
Tokuhara, T., Hattori, N., Ishida, H., Hirai, T., Higashiyama, M., Kodama, K., & Miyake, M. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-0338 · Cited by 111 · see citing works
Biomarker-activatable probes based on smart AIEgens for fluorescence and optoacoustic imaging
Ouyang, J., Sun, L., Zeng, F., & Wu, S. (2022) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2022.214438 · Cited by 108 · see citing works
Self-citationAutomated histological classification of whole-slide images of gastric biopsy specimens
Yoshida, H., Shimazu, T., Kiyuna, T., et al. (2017) · Gastric Cancer · doi:10.1007/s10120-017-0731-8 · Cited by 103 · see citing works
Qi, J., Feng, L., Zhang, X., Zhang, H., Huang, L., Zhou, Y., Zhao, Z., zhao, Z., Duan, X., Xu, F., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-21208-1 · Cited by 101 · see citing works
Emerging contrast agents for multispectral optoacoustic imaging and their biomedical applications
Wu, Y., Zeng, F., Zhao, Y., & Wu, S. (2021) · Chemical Society Reviews · doi:10.1039/d1cs00358e · Cited by 98 · see citing works
Self-citationLi, D., Qu, C., Liu, Q., Wu, Y., Hu, X., Qian, K., Chang, B., He, S., Yuan, Y., Li, Y., et al. (2019) · Advanced Functional Materials · doi:10.1002/adfm.201906343 · Cited by 96 · see citing works
Activatable Rare Earth Near-Infrared-II Fluorescence Ratiometric Nanoprobes
Sun, Z., Huang, H., Zhang, R., Yang, X., Yang, H., Li, C., Zhang, Y., & Wang, Q. (2021) · Nano Letters · doi:10.1021/acs.nanolett.1c01962 · Cited by 96 · see citing works
Li, S., Ma, Q., Wang, C., et al. (2022) · Analytical Chemistry · doi:10.1021/acs.analchem.1c05154 · Cited by 95 · see citing works
Huang, Y. X., Qi, Y., Zhan, C., Zeng, F., & Wu, S. (2019) · Analytical Chemistry · doi:10.1021/acs.analchem.9b00107 · Cited by 91 · see citing works
Self-citationRatiometric Photoacoustic Molecular Imaging for Methylmercury Detection in Living Subjects
Liu, Y., Wang, S., Ma, Y., et al. (2017) · Advanced Materials · doi:10.1002/adma.201606129 · Cited by 90 · see citing works
Tian, Y., Li, Y., Jiang, W., Zhou, D.-Y., Fei, J., & Li, C. (2019) · Analytical Chemistry · doi:10.1021/acs.analchem.9b02857 · Cited by 90 · see citing works
Photoacoustic Imaging of Nanoparticle Transport in the Kidneys at High Temporal Resolution
Jiang, X., Du, B., Tang, S., et al. (2019) · Angewandte Chemie International Edition · doi:10.1002/anie.201901525 · Cited by 89 · see citing works
He, X., Xu, Y., Shi, W. S., & Ma, H. (2017) · Analytical Chemistry · doi:10.1021/acs.analchem.7b00021 · Cited by 84 · see citing works
Sun, L., Ouyang, J., Zeng, F., & Wu, S. (2022) · Biomaterials · doi:10.1016/j.biomaterials.2022.121468 · Cited by 84 · see citing works
Self-citationZeng, Z., Ouyang, J., Sun, L., Zeng, C., Zeng, F., & Wu, S. (2020) · Analytical Chemistry · doi:10.1021/acs.analchem.0c01596 · Cited by 80 · see citing works
Self-citationHudson, S. V., Huang, J. S., Yin, W., et al. (2014) · Cancer Research · doi:10.1158/0008-5472.can-14-1656 · Cited by 72 · see citing works
Accurate Fluorescence Diagnosis of Cancer Based on Sequential Detection of Hydrogen Sulfide and pH
She, Z., Wang, W., Jiang, W., et al. (2021) · Analytical Chemistry · doi:10.1021/acs.analchem.1c02449 · Cited by 62 · see citing works
Genetically encoded photo-switchable molecular sensors for optoacoustic and super-resolution imaging
Mishra, K., Fuenzalida-Werner, J. P., Pennacchietti, F., Janowski, R., Chmyrov, A., Huang, Y., Zakian, C. M., Klemm, U., Testa, I., Niessing, D., et al. (2021) · Nature Biotechnology · doi:10.1038/s41587-021-01100-5 · Cited by 61 · see citing works
Inhibition of c-Met Reduces Lymphatic Metastasis in RIP-Tag2 Transgenic Mice
Sennino, B., Ishiguro-Oonuma, T., Schriver, B. J., Christensen, J. G., & McDonald, D. M. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-2160 · Cited by 60 · see citing works
Dissemination from a Solid Tumor: Examining the Multiple Parallel Pathways
Katt, M. E., Wong, A. D., & Searson, P. C. (2018) · Trends in cancer · doi:10.1016/j.trecan.2017.12.002 · Cited by 58 · see citing works
Wu, Y., Chen, J., Sun, L., et al. (2019) · Advanced Functional Materials · doi:10.1002/adfm.201807960 · Cited by 55 · see citing works
Self-citationLiu, Y., Xu, C., Liu, H., Teng, L., Huan, S., Yuan, L., & Zhang, X. (2021) · Analytical Chemistry · doi:10.1021/acs.analchem.1c00280 · Cited by 48 · see citing works
Bai, F., Du, W., Liu, X., Su, L., Li, Z., Chen, T., Ge, X., Li, Q., Yang, H., & Song, J. (2021) · Analytical Chemistry · doi:10.1021/acs.analchem.1c02238 · Cited by 47 · see citing works
Zhang, X., Jiang, C., He, T., et al. (2022) · Analytical Chemistry · doi:10.1021/acs.analchem.1c04891 · Cited by 42 · see citing works
Chen, J., Fang, Y., Sun, L., et al. (2020) · Chemical Communications · doi:10.1039/d0cc04635c · Cited by 35 · see citing works
Self-citationOrthogonal Multiplexed NIR-II Imaging with Excitation-Selective Lanthanide-Based Nanoparticles
Xu, H., Yang, Y., Lu, L., Yang, Y., Zhang, Z., Zhao, C., Zhang, F., & Fan, Y. (2022) · Analytical Chemistry · doi:10.1021/acs.analchem.1c05253 · Cited by 30 · see citing works
Chen, J., Chen, L., Fang, Y., Zeng, F., & Wu, S. (2022) · Cell Reports Physical Science · doi:10.1016/j.xcrp.2021.100570 · Cited by 29 · see citing works
Self-citationTwo-Photon Supramolecular Nanoplatform for Ratiometric Bioimaging
Zhang, C., Wang, P., Yin, X., Liu, H., Yang, Y., Cheng, L., Song, G., & Zhang, X. (2019) · Analytical Chemistry · doi:10.1021/acs.analchem.9b01455 · Cited by 26 · see citing works
In vitro and in vivo activity of melflufen (J1) in lymphoma
Delforoush, M., Strese, S., Wickström, M., et al. (2016) · BMC Cancer · doi:10.1186/s12885-016-2299-9 · Cited by 21 · see citing works
Wang, X., Yang, L., Liu, W., Zhang, Y., Guo, F., Zhang, L., Cui, M., Liu, S., & Wu, R. (2018) · Molecular Medicine Reports · doi:10.3892/mmr.2018.8402 · Cited by 16 · see citing works
Qin, Z., Ren, T., Zhou, H., Zhang, X., He, L., Li, Z., Zhang, X., & Yuan, L. (2022) · Angewandte Chemie · doi:10.1002/ange.202201541 · Cited by 15 · see citing works
Liapis, E., Karlas, A., Klemm, U., & Ntziachristos, V. (2021) · Theranostics · doi:10.7150/thno.56173 · Cited by 14 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Organic small-molecule NIR-II fluorophores for tumor phototheranostics
Xiang, D., Wang, Z., Zheng, H., Tang, Y., & Li, Q. (2026) · Light: Science & Applications · doi:10.1038/s41377-026-02212-w · Cited by 22 · see citing works
“Regrettably, this strategy has not effectively addressed the issue of low molar extinction coef fi cient in the NIR-II region 223 .”
- Authors
- Chen, J., Chen, L., Zeng, F., & Wu, S.
- Affiliations
- State Key Laboratory of Luminescent Materials and Devices (CN)
- Corresponding author
- Zeng, Fang
- Wu, Shuizhu
- Venue
- Analytical Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2022-06-03
- Volume
- 94
- Issue
- 23
- Pages
- 8449-8457
- ISSN
- 0003-2700 (ISSN-L)
- 1520-6882
- OpenAlex
- W4282054194
- Cited by
- 50
- References
- 61
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 16 · 2023: 15 · 2022: 5
- FWCI
- 3.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Analytical Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (21788102, 21875069)
- Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates (2019B030301003)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Physical Sciences › Chemistry › Spectroscopy › Molecular Sensors and Ion Detection
- Physical Sciences › Materials Science › Materials Chemistry › Luminescence and Fluorescent Materials
- Keywords
- CD13, lymph node metastasis, image-guided surgery, NIR-II fluorescence imaging, photoacoustic imaging, multispectral optoacoustic tomography, tricyanofuran, xanthene, bovine serum albumin, tumor resection
- MeSH terms
- Alanine, Humans, Lymphatic Metastasis, Molecular Probes, CD13 Antigens, Spectroscopy, Near-Infrared, Optical Imaging
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
