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Research Article

Naked-eye visualization of lymph nodes using fluorescence nanoprobes in non-human primate-animal models

Xiaoyuan Ji1,2,§, Binbin Chu1,§, Xiaofeng Wu4,§, Zhiming Xia3,5,§, Airui Jiang1, Chenyu Wang1, Zhiming Chen4, Danni Zhong3,5, Qiaolin Wei6, Bin Song1, Wanlin Li5, Yiling Zhong1, Houyu Wang1, Fenglin Dong4( ), Min Zhou3,5( ), Yao He1,7,8( )
Suzhou Key Laboratory of Nanotechnology and Biomedicine, Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, Suzhou 215123, China
School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
Zhejiang University-University of Edinburgh Institute (ZJU-UoE Institute), Zhejiang University, Haining 314400, China
Department of Ultrasound, the First Affiliated Hospital of Soochow University, Suzhou 215006, China
State Key Laboratory (SKL) of Biobased Transportation Fuel Technology, Zhejiang University, Hangzhou 310027, China
School of Pharmacy, Hangzhou Normal University, Hangzhou 311121, China
Macao Translational Medicine Center, Macau University of Science and Technology, Taipa 999078, Macau, China
Macao Institute of Materials Science and Engineering, Macau University of Science and Technology, Taipa 999078, Macau, China

§ Xiaoyuan Ji, Binbin Chu, Xiaofeng Wu, and Zhiming Xia contributed equally to this work.

Show Author Information

Graphical Abstract

We herein present a pioneering demonstration of nanomaterials based optical imaging-guided surgical operation by using macaques as non-human primate-animal models. Typically, taking advantages of strong and stable fluorescence of small-sized (diameter: ~ 5 nm) silicon-based nanoparticles (SiNPs), lymphatic drainage patterns can be vividly visualized in a real-time manner, and lymph nodes (LNs) are able to be sensitively detected and precisely excised from small animal models (e.g., rats and rabbits) to non-human primate animal models (e.g., cynomolgus macaque (Macaca fascicularis) and rhesus macaque (Macaca mulatta)).

Abstract

Despite sufficient studies performed in non-primate animal models, there exists scanty information obtained from pilot trials in non-human primate animal models, severely hindering nanomaterials moving from basic research into clinical practice. We herein present a pioneering demonstration of nanomaterials based optical imaging-guided surgical operation by using macaques as a typical kind of non-human primate-animal models. Typically, taking advantages of strong and stable fluorescence of the small-sized (diameter: ~ 5 nm) silicon-based nanoparticles (SiNPs), lymphatic drainage patterns can be vividly visualized in a real-time manner, and lymph nodes (LN) are able to be sensitively detected and precisely excised from small animal models (e.g., rats and rabbits) to non-human primate animal models (e.g., cynomolgus macaque (Macaca fascicularis) and rhesus macaque (Macaca mulatta)). Compared to clinically used invisible near-infrared (NIR) lymphatic tracers (i.e., indocyanine green (ICG); etc.), we fully indicate that the SiNPs feature unique advantages for naked-eye visible fluorescence-guided surgical operation in long-term manners. Thorough toxicological analysis in macaque models further provides confirming evidence of favorable biocompatibility of the SiNPs probes. We expect that our findings would facilitate the translation of nanomaterials from the laboratory to the clinic, especially in the field of cancer treatment.

Keywords

fluorescent silicon nanoparticleslymph nodereal-timenaked-eye visualizationmacaque models

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References

[1]

Liang, S.; Yao, J. J.; Liu, D.; Rao, L.; Chen, X. Y.; Wang, Z. H. Harnessing nanomaterials for cancer sonodynamic immunotherapy. Adv. Mater. 2023, 35, 2211130.
Crossref Google Scholar
[2]

Shi, Y. X.; Su, W.; Yuan, F. L.; Yuan, T.; Song, X. Z.; Han, Y. Y.; Wei, S. Y.; Zhang, Y.; Li, Y. C.; Li, X. H. et al. Carbon dots for electroluminescent light-emitting diodes: Recent progress and future prospects. Adv. Mater. 2023, 35, 2210699.
Crossref Google Scholar
[3]

Semeniak, D.; Cruz, D. F.; Chilkoti, A.; Mikkelsen, M. H. Plasmonic fluorescence enhancement in diagnostics for clinical tests at point-of-care: A review of recent technologies. Adv. Mater. 2023, 35, 2107986.
Crossref Google Scholar
[4]

Qiu, X. C.; Zhu, X. J.; Su, X. L.; Xu, M.; Yuan, W.; Liu, Q. Y.; Xue, M.; Liu, Y. W.; Feng, W.; Li, F. Y. Near-infrared upconversion luminescence and bioimaging in vivo based on quantum dots. Adv. Sci. (Weinh.) 2019, 6, 1801834.
Crossref Google Scholar
[5]

Chu, B. B.; Wang, H. Y.; He, Y. Fluorescent silicon-based nanomaterials imaging technology in diseases. Chem. Res. Chin. Univ. 2021, 37, 880–888.
Crossref Google Scholar
[6]

Sun, R.; Liu, M. Z.; Lu, J. P.; Chu, B. B.; Yang, Y. M.; Song, B.; Wang, H. Y.; He, Y. Bacteria loaded with glucose polymer and photosensitive ICG silicon-nanoparticles for glioblastoma photothermal immunotherapy. Nat. Commun. 2022, 13, 5127.
Crossref Google Scholar
[7]

Hong, G. S.; Diao, S.; Antaris, A. L.; Dai, H. J. Carbon nanomaterials for biological imaging and nanomedicinal therapy. Chem. Rev. 2015, 115, 10816–10906.
Crossref Google Scholar
[8]

Ðorđević, L.; Arcudi, F.; Cacioppo, M.; Prato, M. A multifunctional chemical toolbox to engineer carbon dots for biomedical and energy applications. Nat. Nanotechnol. 2022, 17, 112–130.
Crossref Google Scholar
[9]

Loh, K. P.; Ho, D.; Chiu, G. N. C.; Leong, D. T.; Pastorin, G.; Chow, E. K. H. Clinical applications of carbon nanomaterials in diagnostics and therapy. Adv. Mater. 2018, 30, 1802368.
Crossref Google Scholar
[10]

Chen, Y.; Wang, S. F.; Zhang, F. Near-infrared luminescence high-contrast in vivo biomedical imaging. Nat. Rev. Bioeng. 2023, 1, 60–78.
Crossref Google Scholar
[11]

Fan, Y.; Wang, P. Y.; Lu, Y. Q.; Wang, R.; Zhou, L.; Zheng, X. L.; Li, X. M.; Piper, J. A.; Zhang, F. Lifetime-engineered NIR-II nanoparticles unlock multiplexed in vivo imaging. Nat. Nanotechnol. 2018, 13, 941–946.
Crossref Google Scholar
[12]

Pei, P.; Chen, Y.; Sun, C. X.; Fan, Y.; Yang, Y. M.; Liu, X.; Lu, L. F.; Zhao, M. Y.; Zhang, H. X.; Zhao, D. Y. et al. X-ray-activated persistent luminescence nanomaterials for NIR-II imaging. Nat. Nanotechnol. 2021, 16, 1011–1018.
Crossref Google Scholar
[13]

Wang, T.; Wang, S. F.; Liu, Z. Y.; He, Z. Y.; Yu, P.; Zhao, M. Y.; Zhang, H. X.; Lu, L. F.; Wang, Z. X.; Wang, Z. Y. et al. A hybrid erbium (III)-bacteriochlorin near-infrared probe for multiplexed biomedical imaging. Nat. Mater. 2021, 20, 1571–1578.
Crossref Google Scholar
[14]

Yang, Y. W.; Chen, Y.; Pei, P.; Fan, Y.; Wang, S. F.; Zhang, H. X.; Zhao, D. Y.; Qian, B. Z.; Zhang, F. Fluorescence-amplified nanocrystals in the second near-infrared window for in vivo real-time dynamic multiplexed imaging. Nat. Nanotechnol. 2023, 18, 1195–1204.
Crossref Google Scholar
[15]

Weissleder, R. Molecular imaging in cancer. Science 2006, 312, 1168–1171.
Crossref Google Scholar
[16]

Liu, J.; Chen, C.; Ji, S. L.; Liu, Q.; Ding, D.; Zhao, D.; Liu, B. Long wavelength excitable near-infrared fluorescent nanoparticles with aggregation-induced emission characteristics for image-guided tumor resection. Chem. Sci. 2017, 8, 2782–2789.
Crossref Google Scholar
[17]

Antaris, A. L.; Chen, H.; Cheng, K.; Sun, Y.; Hong, G. S.; Qu, C. R.; Diao, S.; Deng, Z. X.; Hu, X. M.; Zhang, B. et al. A small-molecule dye for NIR-II imaging. Nat. Mater. 2016, 15, 235–242.
Crossref Google Scholar
[18]

Hong, G. S.; Antaris, A. L.; Dai, H. J. Near-infrared fluorophores for biomedical imaging. Nat. Biomed. Eng. 2017, 1, 0010.
Crossref Google Scholar
[19]

Toh, U.; Iwakuma, N.; Mishima, M.; Okabe, M.; Nakagawa, S.; Akagi, Y. Navigation surgery for intraoperative sentinel lymph node detection using indocyanine green (ICG) fluorescence real-time imaging in breast cancer. Breast Cancer Res. Treat. 2015, 153, 337–344.
Crossref Google Scholar
[20]

De Gooyer, J. M.; Elekonawo, F. M. K.; Bremers, A. J. A.; Boerman, O. C.; Aarntzen, E. H. J. G.; De Reuver, P. R.; Nagtegaal, I. D.; Rijpkema, M.; De Wilt, J. H. W. Multimodal CEA-targeted fluorescence and radioguided cytoreductive surgery for peritoneal metastases of colorectal origin. Nat. Commun. 2022, 13, 2621.
Crossref Google Scholar
[21]

Mitragotri, S.; Anderson, D. G.; Chen, X. Y.; Chow, E. K.; Ho, D.; Kabanov, A. V.; Karp, J. M.; Kataoka, K.; Mirkin, C. A.; Petrosko, S. H. et al. Accelerating the translation of nanomaterials in biomedicine. ACS Nano 2015, 9, 6644–6654.
Crossref Google Scholar
[22]

Ioannidis, J. P. A.; Kim, B. Y. S.; Trounson, A. How to design preclinical studies in nanomedicine and cell therapy to maximize the prospects of clinical translation. Nat. Biomed. Eng. 2018, 2, 797–809.
Crossref Google Scholar
[23]

Dawidczyk, C. M.; Russell, L. M.; Searson, P. C. Recommendations for benchmarking preclinical studies of nanomedicines. Cancer Res. 2015, 75, 4016–4020.
Crossref Google Scholar
[24]

Yong, K. T.; Law, W. C.; Hu, R.; Ye, L.; Liu, L. W.; Swihart, M. T.; Prasad, P. N. Nanotoxicity assessment of quantum dots: From cellular to primate studies. Chem. Soc. Rev. 2013, 42, 1236–1250.
Crossref Google Scholar
[25]

Stead, S. O.; Kireta, S.; McInnes, S. J. P.; Kette, F. D.; Sivanathan, K. N.; Kim, J.; Cueto-Diaz, E. J.; Cunin, F.; Durand, J. O.; Drogemuller, C. J. et al. Murine and non-human primate dendritic cell targeting nanoparticles for in vivo generation of regulatory T-cells. ACS Nano 2018, 12, 6637–6647.
Crossref Google Scholar
[26]

Moore, L.; Yang, J. Y.; Lan, T. T. H.; Osawa, E.; Lee, D. K.; Johnson, W. D.; Xi, J. Z.; Chow, E. K. H.; Ho, D. Biocompatibility assessment of detonation nanodiamond in non-human primates and rats using histological, hematologic, and urine analysis. ACS Nano 2016, 10, 7385–7400.
Crossref Google Scholar
[27]

Jennings, C. G.; Landman, R.; Zhou, Y.; Sharma, J.; Hyman, J.; Movshon, J. A.; Qiu, Z. L.; Roberts, A. C.; Roe, A. W.; Wang, X. Q. et al. Opportunities and challenges in modeling human brain disorders in transgenic primates. Nat. Neurosci. 2016, 19, 1123–1130.
Crossref Google Scholar
[28]

Saga, Y.; Hoshi, E.; Tremblay, L. Roles of multiple Globus pallidus territories of monkeys and humans in motivation, cognition and action: An anatomical, physiological and pathophysiological review. Front. Neuroanat. 2017, 11, 30.
Crossref Google Scholar
[29]

Y.; Xu, Y. J.; Zhang, G. B.; Ling, D. S.; Wang, M. Q.; Zhou, Y.; Wu, Y. D.; Wu, T.; Hackett, M. J.; Kim, B. H. et al. Iron oxide nanoclusters for T1 magnetic resonance imaging of non-human primates. Nat. Biomed. Eng. 2017, 1, 637–643.
Crossref Google Scholar
[30]

Xu, J.; Yu, M. X.; Peng, C. Q.; Carter, P.; Tian, J.; Ning, X. H.; Zhou, Q. H.; Tu, Q.; Zhang, G.; Dao, A. et al. Dose dependencies and biocompatibility of renal clearable gold nanoparticles: From mice to non-human primates. Angew. Chem., Int. Ed. 2018, 57, 266–271.
Crossref Google Scholar
[31]

Yoo, C. H.; DuBois, J. M.; Wang, L.; Tang, Y. J.; Hou, L.; Xu, H.; Chen, J. H.; Liang, S. H.; Izquierdo-Garcia, D.; Wey, H. Y. Preliminary Exploration of pseudo-CT-based attenuation correction for simultaneous PET/MRI brain imaging in nonhuman primates. ACS Omega 2023, 8, 45438–45446.
Crossref Google Scholar
[32]

Padera, T. P.; Kadambi, A.; Di Tomaso, E.; Carreira, C. M.; Brown, E. B.; Boucher, Y.; Choi, N. C.; Mathisen, D.; Wain, J.; Mark, E. J.; et al. Lymphatic metastasis in the absence of functional Intratumor Lymphatics. Science 2002, 296, 1883–1886.
Crossref Google Scholar
[33]

Swartz, M. A.; Lund, A. W. Lymphatic and interstitial flow in the tumour microenvironment: Linking mechanobiology with immunity. Nat. Rev. Cancer 2012, 12, 210–219.
Crossref Google Scholar
[34]

Stoffels, I.; Morscher, S.; Helfrich, I.; Hillen, U.; Leyh, J.; Burton, N. C.; Sardella, T. C. P.; Claussen, J.; Poeppel, T. D.; Bachmann, H. S. et al. Metastatic status of sentinel lymph nodes in melanoma determined noninvasively with multispectral optoacoustic imaging. Sci. Transl. Med. 2015, 7, 317ra199.
Crossref Google Scholar
[35]

Zhong, Y. L.; Song, B.; Shen, X. B.; Guo, D. X.; He, Y. Fluorescein sodium ligand-modified silicon nanoparticles produce ultrahigh fluorescence with robust pH- and photo-stability. Chem. Commun. 2019, 55, 365–368.
Crossref Google Scholar
[36]

Pang, Z. Y.; Yan, W. X.; Yang, J.; Li, Q. Z.; Guo, Y.; Zhou, D. J.; Jiang, X. Y. Multifunctional gold nanoclusters for effective targeting, near-infrared fluorescence imaging, diagnosis, and treatment of cancer lymphatic metastasis. ACS Nano 2022, 16, 16019–16037.
Crossref Google Scholar
[37]

Swartz, M. A. The physiology of the lymphatic system. Adv. Drug Deliv. Rev. 2001, 50, 3–20.
Crossref Google Scholar
[38]

Pan, D.; Cai, X.; Yalaz, C.; Senpan, A.; Omanakuttan, K.; Wickline, S. A.; Wang, L. V.; Lanza, G. M. Photoacoustic sentinel lymph node imaging with self-assembled copper neodecanoate nanoparticles. ACS Nano 2012, 6, 1260–1267.
Crossref Google Scholar
[39]

Vahrmeijer, A. L.; Hutteman, M.; Van Der Vorst, J. R.; Van De Velde, C. J. H.; Frangioni, J. V. Image-guided cancer surgery using near-infrared fluorescence. Nat. Rev. Clin. Oncol. 2013, 10, 507–518.
Crossref Google Scholar
[40]

Dunne, A. A.; Plehn, S.; Schulz, S.; Levermann, A.; Ramaswamy, A.; Lippert, B. M.; Werner, J. A. Lymph node topography of the head and neck in New Zealand White rabbits. Lab. Anim. 2003, 37, 37–43.
Crossref Google Scholar
[41]

G. H.; Giuliano, A. E.; Somerfield, M. R.; Benson III, A. B.; Bodurka, D. C.; Burstein, H. J.; Cochran, A. J.; Cody III, H. S.; Edge, S. B.; Galper, S. et al. American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer. J. Clin. Oncol. 2005, 23, 7703–7720.
Crossref Google Scholar
[42]

McMasters, K. M.; Tuttle, T. M.; Carlson, D. J.; Brown, C. M.; Noyes, R. D.; Glaser, R. L.; Vennekotter, D. J.; Turk, P. S.; Tate, P. S.; Sardi, A. et al. Sentinel lymph node biopsy for breast cancer: A suitable alternative to routine axillary dissection in multi-institutional practice when optimal technique is used. J. Clin. Oncol. 2000, 18, 2560–2566.
Crossref Google Scholar
[43]

Lyman, G. H.; Temin, S.; Edge, S. B.; Newman, L. A.; Turner, R. R.; Weaver, D. L.; Benson, A. B.; Bosserman, L. D.; Burstein, H. J.; Cody, H. et al. Sentinel lymph node biopsy for patients with early-stage breast cancer: American society of clinical oncology clinical practice guideline update. J. Clin. Oncol. 2014, 32, 1365–1383.
Crossref Google Scholar
[44]

Kim, C. Y.; Lee, H. S.; Han, S. C.; Heo, J. D.; Kwon, M. S.; Ha, C. S.; Han, S. S. Hematological and serum biochemical values in cynomolgus monkeys anesthetized with ketamine hydrochloride. J. Med. Primatol. 2005, 34, 96–100.
Crossref Google Scholar
[45]

Park, H. K.; Cho, J. W.; Lee, B. S.; Park, H.; Han, J. S.; Yang, M. J.; Im, W. J.; Park, D. Y.; Kim, W. J.; Han, S. C. et al. Reference values of clinical pathology parameters in cynomolgus monkeys ( Macaca fascicularis) used in preclinical studies. Lab. Anim. Res. 2016, 32, 79–86.
Crossref Google Scholar
[46]

Krag, D. N.; Anderson, S. J.; Julian, T. B.; Brown, A. M.; Harlow, S. P.; Costantino, J. P.; Ashikaga, T.; Weaver, D. L.; Mamounas, E. P.; Jalovec, L. M. et al. Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: Overall survival findings from the NSABP B-32 randomised phase 3 trial. Lancet Oncol. 2010, 11, 927–933.
Crossref Google Scholar
[47]

Akay, C. L.; Albarracin, C.; Torstenson, T.; Bassett, R.; Mittendorf, E. A.; Yi, M.; Kuerer, H. M.; Babiera, G. V.; Bedrosian, I.; Hunt, K. K. et al. Factors impacting the accuracy of intra-operative evaluation of sentinel lymph nodes in breast cancer. Breast J. 2018, 24, 28–34.
Crossref Google Scholar
[48]

Han, J. F.; Zhang, L.; Cui, M. Y.; Su, Y. Y.; He, Y. Rapid and accurate detection of lymph node metastases enabled through fluorescent silicon nanoparticles-based exosome probes. Anal. Chem. 2021, 93, 10122–10131.
Crossref Google Scholar
Nano Research
Volume 17 Issue 8,
August 2024
Pages 7404-7414
DOI: 10.1007/s12274-024-6683-5
Cite this article:
Ji X, Chu B, Wu X, et al. Naked-eye visualization of lymph nodes using fluorescence nanoprobes in non-human primate-animal models. Nano Research, 2024, 17(8): 7404-7414. https://doi.org/10.1007/s12274-024-6683-5
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Received: 21 February 2024
Revised: 01 April 2024
Accepted: 03 April 2024
Published: 27 June 2024
© Tsinghua University Press 2024
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