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Ultrabright near-infrared fluorescent DNA frameworks for near-single-cell cancer imaging

Nature Photonics volume 19, pages 79–88 (2025)Cite this article

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Abstract

Cancer imaging approaching single-cell levels is highly desirable for studying in vivo cell migration and cancer metastasis. However, current imaging probes struggle to simultaneously achieve high sensitivity, deep-tissue penetration and tissue specificity. Here we report size- and shape-resolved fluorescent DNA framework (FDF) dots with tail emission in the second near-infrared window (1,000–1,700 nm, NIR-II), which enable near-single-cell-level, tumour-targeting deep-tissue (~1 cm) NIR-II imaging in tumour-bearing mouse models. The construction of DNA frameworks with embedded hydrophobic nanocavity results in the non-covalent encapsulation of a designed NIR-Ib (900–1,000 nm) probe (dye Sq964). The FDF dots exhibit high water solubility, brightness and photostability. We find that the stable tumour retention of FDF dots with enhanced signal intensity arises from their shape-dependent accumulation in tumour cells. FDF-dot-based cancer imaging reveals in vivo sensitivity down to ~40 tumour cells, high tumour-to-normal tissue ratios up to ~26 and long-term imaging over 11 days. We also demonstrate NIR-II-image-guided breast cancer surgery with the complete excision of metastases with a minimum size of ~53 μm (~20 cells).

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Fig. 1: NIR-Ib FDF dots for cancer imaging and image-guided tumour surgery.
Fig. 2: Optical properties of FDF dots.
Fig. 3: Versatility of DNA frameworks for encapsulation of diverse dyes.
Fig. 4: Breast cancer cell labelling with FDF dots.
Fig. 5: In vivo imaging of FDF-dot-labelled breast cancer cells.
Fig. 6: NIR-image-guided surgery of metastases.

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Data availability

The data that support the findings of this study are available within the Article and its Supplementary Information. Additional data and files are available from the corresponding authors upon reasonable request. Source data are provided with this paper.

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Acknowledgements

We thank F. Zhang (Fudan University) and Q. Wang (Suzhou Institute of Nano-Tech and Nano-Bionics) for the NIR imaging assistance. This work was supported by the National Key R&D Program of China (2023YFC3404200 to Y.Z.), the National Natural Science Foundation of China (T2188102 to C.F., 21991134 to C.F., 22325406 to J.L. and 12305400 to Q.Y.), 2022 Shanghai ‘Science and Technology Innovation Action Plan’ Fundamental Research Project (22JC1401203 to Y.Z.) and the Xiangfu Lab Research Project (XF012022E0100 to C.F.). We would like to dedicate this paper to C.Z., who unfortunately passed away just before this paper was revised. C.Z. played an essential role in the research described here and he is greatly missed.

Author information

Author notes

  1. Deceased: Chunchang Zhao.

  2. These authors contributed equally: Xia Liu, Ben Shi, Yue Gao, Shitai Zhu.

Authors and Affiliations

  1. Institute of Materiobiology, College of Sciences, Shanghai University, Shanghai, China

    Xia Liu, Lihua Wang, Jiang Li & Ying Zhu

  2. Xiangfu Laboratory, Jiashan, China

    Xia Liu & Qinglong Yan

  3. Key Laboratory for Advanced Materials and Feringa Nobel Prize Scientist Joint Research Center, Institute of Fine Chemicals, School of Chemistry and Molecular Engineering, Frontiers Science Center for Materiobiology and Dynamic Chemistry, East China University of Science and Technology, Shanghai, China

    Ben Shi, Chunchang Zhao & He Tian

  4. CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China

    Yue Gao, Shitai Zhu & Jiye Shi

  5. School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Zhang Jiang Institute for Advanced Study and National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, China

    Xiaoguo Liu, Qian Li & Chunhai Fan

  6. Institute of Chemistry, Hebrew University of Jerusalem, Jerusalem, Israel

    Itamar Willner

  7. Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acids Chemistry and Nanomedicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

    Chunhai Fan

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Contributions

C.F. and Y.Z. directed the research. C.F., Y.Z., J.L., C.Z., Xia Liu and B.S. conceived and designed the experiments. Xia Liu, B.S., Y.G., S.Z., Q.Y. and Xiaoguo Liu carried out the experiments and analysed the data. J.S., Q.L., L.W., J.L., H.T. and I.W. provided suggestions and technical support on the project. J.L., Y.Z. and C.F. wrote and revised the manuscript. All authors discussed the results and commented on the manuscript.

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Correspondence to Chunchang Zhao, Ying Zhu or Chunhai Fan.

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Nature Photonics thanks Xuechuan Hong, Hak Soo Choi and Xiaoyuan Chen for their contribution to the peer review of this work.

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Liu, X., Shi, B., Gao, Y. et al. Ultrabright near-infrared fluorescent DNA frameworks for near-single-cell cancer imaging. Nat. Photon. 19, 79–88 (2025). https://doi.org/10.1038/s41566-024-01543-7

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