Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Protocol
  • Published:

In situ label-free X-ray imaging for visualizing the localization of nanomedicines and subcellular architecture in intact single cells

Nature Protocols volume 19, pages 30–59 (2024)Cite this article

Subjects

Abstract

Understanding the intracellular behaviors of nanomedicines and morphology variation of subcellular architecture impacted by nanomaterial–biology (nano–bio) interactions could help guide the safe-by-design, manufacturing and evaluation of nanomedicines for clinical translation. The in situ and label-free analysis of nano–bio interactions in intact single cells at nanoscale remains challenging. We developed an approach based on X-ray microscopy to directly visualize the 2D or 3D intracellular distribution without labeling at nanometer resolution and analyze the chemical transformation of nanomedicines in situ. Here, we describe an optimized workflow for cell sample preparation, beamline selection, data acquisition and analysis. With several model bionanomaterials as examples, we analyze the localization of nanomedicines in various primary blood cells, macrophages, dendritic cells, monocytes and cancer cells, as well as the morphology of some organelles with soft and hard X-rays. Our protocol has been successfully implemented at three beamline facilities: 4W1A of Beijing Synchrotron Radiation Facility, BL08U1A of Shanghai Synchrotron Radiation Facility and BL07W of the National Synchrotron Radiation Laboratory. This protocol can be completed in ~2–5 d, depending on the cell types, their incubation times with nanomaterials and the selected X-ray beamline. The protocol enables the in situ analysis of the varieties of metal-containing nanomaterials, visualization of intracellular endocytosis, distribution and excretion and corresponding subcellular morphological variation influenced by nanomedicines in cell lines or primary cells by using this universal and robust platform. The results facilitate the understanding of the true principle and mechanism underlying the nano–bio interaction.

Key points

  • An optimized workflow that includes cell sample preparation, hard and soft X-ray beamline selection, data acquisition and analysis for the localization of nanomedicines and the morphology of organelles in primary blood cells, macrophages, dendritic cells, monocytes and cancer cells.

  • The protocol has been implemented at the 4W1A of Beijing Synchrotron Radiation Facility, BL08U1A of Shanghai Synchrotron Radiation Facility and BL07W of the Chinese National Synchrotron Radiation Laboratory.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Soft and hard X-ray imaging of nanomedicines and subcellular architecture in intact cells based on synchrotron radiation facilities as a universal and robust platform.
Fig. 2: Guideline for selection from soft and hard X-ray imaging.
Fig. 3: Overall procedure of soft/hard X-ray imaging.
Fig. 4: Cell samples preparation process.
Fig. 5: Workflow of the cell incubation and sample preservation for cryo-soft X-ray imaging.
Fig. 6: Workflow of the cell incubation and sample preservation for hard X-ray nano-CT imaging and noncryogenic soft X-ray imaging.
Fig. 7: Data acquisition procedure performed at beamline 07W of NSRL.
Fig. 8: Data analysis procedure.
Fig. 9: Cryo-soft X-ray nano-CT imaging applied to investigate intracellular structures and distribution of NPs in cells with native states.
Fig. 10: Hard X-ray TXM imaging used to observe the interactions of NPs with large cells.
Fig. 11: Soft X-ray dual-energy contrast STXM to achieve elemental mapping of intracellular NPs.

Similar content being viewed by others

Data availability

The main data presented in this protocol are available in the primary research papers60,61,62,73. The raw datasets are too large to be shared in the public repository but are available from the corresponding author upon reasonable request.

References

  1. Zhang, C. et al. Progress, challenges, and future of nanomedicine. Nano Today 35, 101008 (2020).

    Article  CAS  Google Scholar 

  2. Poon, W., Kingston, B., Ouyang, B., Ngo, W. & Chan, W. A framework for designing delivery systems. Nat. Nanotechnol. 15, 819–829 (2020).

    Article  CAS  PubMed  Google Scholar 

  3. Bourzac, K. Nanotechnology: carrying drugs. Nature 491, S58–S60 (2012).

    Article  PubMed  Google Scholar 

  4. Gewin, V. Big opportunities in a small world. Nature 460, 540–541 (2009).

    Article  CAS  PubMed  Google Scholar 

  5. Kim, B. Y., Rutka, J. T. & Chan, W. C. Nanomedicine. N. Engl. J. Med. 363, 2434–2443 (2010).

    Article  CAS  PubMed  Google Scholar 

  6. Wang, Y., Cai, R. & Chen, C. The nano–bio interactions of nanomedicines: understanding the biochemical driving forces and redox reactions. Acc. Chem. Res. 52, 1507–1518 (2019).

    Article  CAS  PubMed  Google Scholar 

  7. Cai, R. & Chen, C. The crown and the scepter: roles of the protein corona in nanomedicine. Adv. Mater. 31, 1805740 (2019).

    Article  CAS  Google Scholar 

  8. Bondarenko, O. et al. Nanotoxicology and nanomedicine: the yin and yang of nano–bio interactions for the new decade. Nano Today 39, 101184 (2021).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Monopoli, M. P., Aberg, C., Salvati, A. & Dawson, K. A. Biomolecular coronas provide the biological identity of nanosized materials. Nat. Nanotechnol. 7, 779–786 (2012).

    Article  CAS  PubMed  Google Scholar 

  10. Cao, M. & Chen, C. Bioavailability of nanomaterials: bridging the gap between nanostructures and their bioactivity. Natl Sci. Rev. 9, nwac119 (2022).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Rosenblum, D., Joshi, N., Tao, W., Karp, J. M. & Peer, D. Progress and challenges towards targeted delivery of cancer therapeutics. Nat. Commun. 9, 1410 (2018).

    Article  PubMed Central  PubMed  Google Scholar 

  12. Rennick, J. J., Johnston, A. P. R. & Parton, R. G. Key principles and methods for studying the endocytosis of biological and nanoparticle therapeutics. Nat. Nanotechnol. 16, 266–276 (2021).

    Article  CAS  PubMed  Google Scholar 

  13. Hubbell, J. A., Thomas, S. N. & Swartz, M. A. Materials engineering for immunomodulation. Nature 462, 449–460 (2009).

    Article  CAS  PubMed  Google Scholar 

  14. Stewart, M. P. et al. In vitro and ex vivo strategies for intracellular delivery. Nature 538, 183–192 (2016).

    Article  CAS  PubMed  Google Scholar 

  15. Korangath, P. et al. Nanoparticle interactions with immune cells dominate tumor retention and induce T cell-mediated tumor suppression in models of breast cancer. Sci. Adv. 6, eaay1601 (2020).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Cao, M., Zhang, K., Zhang, S., Wang, Y. & Chen, C. Advanced light source analytical techniques for exploring the biological behavior and fate of nanomedicines. ACS Cent. Sci. 8, 1063–1080 (2022).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Sanchez-Cano, C. et al. X-ray-based techniques to study the nano–bio interface. ACS Nano 15, 3754–3807 (2021).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Chen, C., Li, Y.-F., Qu, Y., Chai, Z. & Zhao, Y. Advanced nuclear analytical and related techniques for the growing challenges in nanotoxicology. Chem. Soc. Rev. 42, 8266–8303 (2013).

    Article  CAS  PubMed  Google Scholar 

  19. Yuan, Q. et al. A 30 nm-resolution hard X-ray microscope with X-ray fluorescence mapping capability at BSEF. J. Synchrotron Rad. 19, 1021–1028 (2012).

    Article  CAS  Google Scholar 

  20. Liu, G., Chen, L. & Guan, Y. Three dimensional imaging of biological samples and nano-materials using soft X-ray microscopy. Microsc. Microanal. 24, 392–393 (2018).

    Article  Google Scholar 

  21. Liu, H. et al. Soft X-ray spectroscopic endstation at beamline 08U1A of Shanghai Synchrotron Radiation Facility. Rev. Sci. Instrum. 90, 043103 (2019).

    Article  PubMed  Google Scholar 

  22. Howells, M., Jacobsen, C., Warwick, T. & Van den Bos, A. in Science of Microscopy (eds P. W. Hawkes & J. C. H. Spence) 835–926 (Springer, 2007).

  23. Uchida, M. et al. Soft X-ray tomography of phenotypic switching and the cellular response to antifungal peptoids in candida albicans. Proc. Natl Acad. Sci. USA 106, 19375–19380 (2009).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Larabell, C. A. & Le Gros, M. A. X-ray tomography generates 3-D reconstructions of the yeast, Saccharomyces cerevisiae, at 60-nm resolution. Mol. Biol. Cell 15, 957–962 (2004).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Guo, A. et al. Quantitative, in situ visualization of intracellular insulin vesicles in pancreatic beta cells. Proc. Natl Acad. Sci. USA 119, e2202695119 (2022).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. White, K. L. et al. Visualizing subcellular rearrangements in intact β cells using soft X-ray tomography. Sci. Adv. 6, eabc8262 (2020).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Krenkel, M. et al. Phase-contrast zoom tomography reveals precise locations of macrophages in mouse lungs. Sci. Rep. 5, 9973 (2015).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Zhang, C. et al. 3D imaging and quantification of the integrin at a single-cell base on a multisignal nanoprobe and synchrotron radiation soft X-ray tomography microscopy. Anal. Chem. 93, 1237–1241 (2021).

    Article  CAS  PubMed  Google Scholar 

  29. Wang, J. et al. Gd-hybridized plasmonic Au-nanocomposites enhanced tumor-interior drug permeability in multimodal imaging-guided therapy. Adv. Mater. 28, 8950–8958 (2016).

    Article  CAS  PubMed  Google Scholar 

  30. Cagno, S. et al. Combined computed nanotomography and nanoscopic X-ray fluorescence imaging of cobalt nanoparticles in caenorhabditis elegans. Anal. Chem. 89, 11435–11442 (2017).

    Article  CAS  PubMed  Google Scholar 

  31. Ding, J. et al. Single-particle analysis for structure and iron chemistry of atmospheric particulate matter. Anal. Chem. 92, 975–982 (2020).

    Article  CAS  PubMed  Google Scholar 

  32. Qu, Y. et al. Full assessment of fate and physiological behavior of quantum dots utilizing caenorhabditis elegans as a model organism. Nano Lett. 11, 3174–3183 (2011).

    Article  CAS  PubMed  Google Scholar 

  33. Okolo, C. A. et al. Sample preparation strategies for efficient correlation of 3D SIM and soft X-ray tomography data at cryogenic temperatures. Nat. Protoc. 16, 2851–2885 (2021).

    Article  CAS  PubMed  Google Scholar 

  34. Bissardon, C. et al. Cell culture on silicon nitride membranes and cryopreparation for synchrotron X-ray fluorescence nano-analysis. J. Vis. Exp. 10, e60461 (2019).

    Google Scholar 

  35. Finney, L. A. & Jin, Q. Preparing adherent cells for X-ray fluorescence imaging by chemical fixation. J. Vis. Exp. 12, e52370 (2015).

    Google Scholar 

  36. Matsuyama, S. et al. Elemental mapping of frozen-hydrated cells with cryo-scanning X-ray fluorescence microscopy. X-Ray Spectrom. 39, 260–266 (2010).

    Article  CAS  Google Scholar 

  37. Jin, Q. et al. Preserving elemental content in adherent mammalian cells for analysis by synchrotron-based X-ray fluorescence microscopy. J. Microsc. 265, 81–93 (2017).

    Article  CAS  PubMed  Google Scholar 

  38. Chen, J. et al. 3D nanoscale imaging of the yeast, Schizosaccharomyces pombe, by full-field transmission X-ray microscopy at 5.4 keV. Anal. Bioanal. Chem. 397, 2117–2121 (2010).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Larabell, C. A. & Nugent, K. A. Imaging cellular architecture with X-rays. Curr. Opin. Struct. Biol. 20, 623–631 (2010).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Zhu, S., Wang, Y. & Chen, C. In situ analysis of the fate and behavior of inorganic nanomaterials in biological systems by synchrotron radiation X-ray probe techniques. Curr. Anal. Chem. 18, 723–738 (2022).

    Article  CAS  Google Scholar 

  41. Zhang, M. et al. Directly observing intracellular nanoparticle formation with nanocomputed tomography. Sci. Adv. 6, eaba3190 (2020).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Wang, J. et al. 3D chemical and elemental imaging by STXM spectrotomography. AIP Conf. Proc. 1365, 215–218 (2011).

    Article  CAS  Google Scholar 

  43. Guo, Z. et al. Biotransformation modulates the penetration of metallic nanomaterials across an artificial blood–brain barrier model. Proc. Natl Acad. Sci. USA 118, e2105245118 (2021).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  44. Jonge, M. D. D. et al. Quantitative 3D elemental microtomography of Cyclotella meneghiniana at 400-nm resolution. Proc. Natl Acad. Sci. USA 107, 15676–15680 (2010).

    Article  PubMed Central  PubMed  Google Scholar 

  45. Kounatidis, I. et al. 3D correlative cryo-structured illumination fluorescence and soft X-ray microscopy elucidates reovirus intracellular release pathway. Cell 182, 515.e17–530.e17 (2020).

    Article  Google Scholar 

  46. Mendonça, L. et al. Correlative multi-scale cryo-imaging unveils SARS-CoV-2 assembly and egress. Nat. Commun. 12, 4629 (2021).

    Article  PubMed Central  PubMed  Google Scholar 

  47. Schrand, A. M., Schlager, J. J., Dai, L. & Hussain, S. M. Preparation of cells for assessing ultrastructural localization of nanoparticles with transmission electron microscopy. Nat. Protoc. 5, 744–757 (2010).

    Article  CAS  PubMed  Google Scholar 

  48. Peddie, C. J. et al. Volume electron microscopy. Nat. Rev. Methods Prim. 2, 51 (2022).

    Article  CAS  Google Scholar 

  49. Heinrich, L. et al. Whole-cell organelle segmentation in volume electron microscopy. Nature 599, 141–146 (2021).

    Article  CAS  PubMed  Google Scholar 

  50. Xu, C. S. et al. An open-access volume electron microscopy atlas of whole cells and tissues. Nature 599, 147–151 (2021).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  51. Huang, B., Bates, M. & Zhuang, X. Super-resolution fluorescence microscopy. Annu. Rev. Biochem. 78, 993–1016 (2009).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  52. Schermelleh, L. et al. Super-resolution microscopy demystified. Nat. Cell Biol. 21, 72–84 (2019).

    Article  CAS  PubMed  Google Scholar 

  53. Thomsen, T., Ayoub, A. B., Psaltis, D. & Klok, H.-A. Fluorescence-based and fluorescent label-free characterization of polymer nanoparticle decorated T cells. Biomacromolecules 22, 190–200 (2021).

    Article  CAS  PubMed  Google Scholar 

  54. Bernhardt, M. et al. Correlative microscopy approach for biology using X-ray holography, X-ray scanning diffraction and sted microscopy. Nat. Commun. 9, 3641 (2018).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  55. Varsano, N. et al. Development of correlative cryo-soft X-ray tomography and stochastic reconstruction microscopy. A study of cholesterol crystal early formation in cells. J. Am. Chem. Soc. 138, 14931–14940 (2016).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  56. Fan, J. et al. Single-pulse enhanced coherent diffraction imaging of bacteria with an X-ray free-electron laser. Sci. Rep. 6, 34008 (2016).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  57. Seibert, M. M. et al. Single mimivirus particles intercepted and imaged with an X-ray laser. Nature 470, 78–81 (2011).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  58. van der Schot, G. et al. Imaging single cells in a beam of live cyanobacteria with an X-ray laser. Nat. Commun. 6, 5704 (2015).

    Article  PubMed  Google Scholar 

  59. Kimura, T. et al. Imaging live cell in micro-liquid enclosure by X-ray laser diffraction. Nat. Commun. 5, 3052 (2014).

    Article  PubMed  Google Scholar 

  60. Cao, M. et al. Molybdenum derived from nanomaterials incorporates into molybdenum enzymes and affects their activities in vivo. Nat. Nanotechnol. 16, 708–716 (2021).

    Article  CAS  PubMed  Google Scholar 

  61. Zhang, G. et al. A nanomaterial targeting the spike protein captures SARS-CoV-2 variants and promotes viral elimination. Nat. Nanotechnol. 17, 993–1003 (2022).

    Article  CAS  PubMed  Google Scholar 

  62. Wang, Y. et al. Engineering a self-navigated MnARK nanovaccine for inducing potent protective immunity against novel coronavirus. Nano Today 38, 101139 (2021).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  63. Chen, Z. et al. Polyhydroxylated metallofullerenols stimulate IL-1β secretion of macrophage through TLRs/MyD88/NF-κB pathway and NLRP3 inflammasome activation. Small 10, 2362–2372 (2014).

    Article  CAS  PubMed  Google Scholar 

  64. Cao, M. et al. Gadolinium(III)-chelated silica nanospheres integrating chemotherapy and photothermal therapy for cancer treatment and magnetic resonance imaging. ACS Appl. Mater. Interfaces 7, 25014–25023 (2015).

    Article  CAS  PubMed  Google Scholar 

  65. Cao, M., Li, J., Tang, J., Chen, C. & Zhao, Y. Gold nanomaterials in consumer cosmetics nanoproducts: analyses, characterization, and dermal safety assessment. Small 12, 5488–5496 (2016).

    Article  CAS  PubMed  Google Scholar 

  66. Bai, H. et al. Precise correlative method of cryo-SXT and cryo-FM for organelle identification. J. Synchrotron Radiat. 27, 176–184 (2020).

    Article  CAS  PubMed  Google Scholar 

  67. Dang, Z. et al. Regulating the synthesis rate and yield of bio-assembled FeS nanoparticles for efficient cancer therapy. Nanoscale 13, 18977–18986 (2021).

    Article  CAS  PubMed  Google Scholar 

  68. Studer, D. et al. Capture of activity-induced ultrastructural changes at synapses by high-pressure freezing of brain tissue. Nat. Protoc. 9, 1480–1495 (2014).

    Article  CAS  PubMed  Google Scholar 

  69. Zhang, X. et al. Ratio-contrast imaging of dual-energy absorption for element mapping with a scanning transmission X-ray microscope. J. Synchrotron. Rad 17, 804–809 (2010).

    CAS  Google Scholar 

  70. Yao, S. et al. Three-dimensional ultrastructural imaging reveals the nanoscale architecture of mammalian cells. IUCrJ 5, 141–149 (2018).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  71. Peng, M. W. et al. Quantitative three-dimensional nondestructive imaging of whole anaerobic ammonium-oxidizing bacteria. J. Synchrotron Radiat. 27, 753–761 (2020).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  72. Beucher, S. & Meyer, F. in Mathematical Morphology in Image Processing (ed. Dougherty, E. R.) 433–481 (Marcel Dekker, 1993).

  73. Wang, L. et al. Use of synchrotron radiation-analytical techniques to reveal chemical origin of silver-nanoparticle cytotoxicity. ACS Nano 9, 6532–6547 (2015).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work has received financial support from the National Key R&D Program of China (2021YFA1200900, 2022YFA1603701); the National Natural Science Foundation of China (22027810, U2032107); the Strategic Priority Research Program of Chinese Academy of Sciences (XDB36000000); CAMS Innovation Fund for Medical Sciences (CIFMS 2019-I2M-5-018), the National Postdoctoral Program for Innovative Talents (BX2021088) and Project funded by China Postdoctoral Science Foundation (2021M700977). The institutionalized scientific research platform relies on Beijing Synchrotron Radiation Facility of Chinese Academy of Sciences.

Author information

Author notes

  1. These authors contributed equally: Mingjing Cao, Yaling Wang.

Authors and Affiliations

  1. CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing, China

    Mingjing Cao, Yaling Wang, Liming Wang, Yuecong Guo & Chunying Chen

  2. CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and Beijing Synchrotron Radiation Facility, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, China

    Liming Wang, Kai Zhang & Chunying Chen

  3. National Synchrotron Radiation Laboratory, University of Science and Technology of China, Hefei, China

    Yong Guan

  4. GBA National Institute for Nanotechnology Innovation, Guangzhou, China

    Chunying Chen

Authors
  1. Mingjing Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yaling Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Liming Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kai Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yong Guan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yuecong Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Chunying Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

C.C. conceived the idea, provided guidelines, and reviewed and edited the paper. C.C., M.C. and Y.W. contributed to the protocol development and designed the figures. M.C. conceptualized, wrote and reviewed the paper. Y.W. contributed to editing, structuring and reviewing the paper. L.W., K.Z. and Yo.G. contributed to editing the paper. Y.W. and Yu.G. analyzed the nano-CT data.

Corresponding author

Correspondence to Chunying Chen.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Protocols thanks Gaolin Liang, Vladimir Lobaskin and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Related links

Key references using this protocol

Cao M. et al. Nat. Nanotechnol. 16, 708 (2021): https://doi.org/10.1038/s41565-021-00856-w

Zhang G. et al. Nat. Nanotechnol. 17, 993 (2022): https://doi.org/10.1038/s41565-022-01177-2

Wang Y. et al. Nano Today 38, 101139 (2021): https://doi.org/10.1016/j.nantod.2021.101139

Wang L. et al. ACS Nano 9, 6532 (2015): https://doi.org/10.1021/acsnano.5b02483

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cao, M., Wang, Y., Wang, L. et al. In situ label-free X-ray imaging for visualizing the localization of nanomedicines and subcellular architecture in intact single cells. Nat Protoc 19, 30–59 (2024). https://doi.org/10.1038/s41596-023-00902-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41596-023-00902-y

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing