journal article·2023-05-09Open access

Quantifying Intracellular Nanoparticle Distributions with Three-Dimensional Super-Resolution Microscopy

Vinit Sheth, Xuxin Chen, Evan M. Mettenbrink, Wen Yang, Meredith A. Jones, Ons M’Saad, Abigail G. Thomas, Rylee S. Newport, Emmy Francek, Lin Wang, Alex N. Frickenstein, Nathan D. Donahue, Alyssa Holden, Nathan F. Mjema, Dixy E. Green, Paul L. DeAngelis, Joerg Bewersdorf, Stefan Wilhelm

ACS Nano· Volume 17· Issue 9

Abstract

Super-resolution microscopy can transform our understanding of nanoparticle-cell interactions. Here, we established a super-resolution imaging technology to visualize nanoparticle distributions inside mammalian cells. The cells were exposed to metallic nanoparticles and then embedded within different swellable hydrogels to enable quantitative three-dimensional (3D) imaging approaching electron-microscopy-like resolution using a standard light microscope. By exploiting the nanoparticles' light scattering properties, we demonstrated quantitative label-free imaging of intracellular nanoparticles with ultrastructural context. We confirmed the compatibility of two expansion microscopy protocols, protein retention and pan-expansion microscopy, with nanoparticle uptake studies. We validated relative differences between nanoparticle cellular accumulation for various surface modifications using mass spectrometry and determined the intracellular nanoparticle spatial distribution in 3D for entire single cells. This super-resolution imaging platform technology may be broadly used to understand the nanoparticle intracellular fate in fundamental and applied studies to potentially inform the engineering of safer and more effective nanomedicines.
Source: openalex_inverted_index · Quality: baseline

Research context

OpenAlex topics: Advanced Electron Microscopy Techniques and Applications · Advanced Fluorescence Microscopy Techniques · Photoacoustic and Ultrasonic Imaging

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Stephenson School of Biomedical Engineering, University of Oklahoma, Norman, Oklahoma 73019, United States

School of Electrical and Computer Engineering, University of Oklahoma, Norman, Oklahoma 73019, United States

Department of Cell Biology, Yale School of Medicine, New Haven, Connecticut 06510, United States

Department of Biomedical Engineering, Yale University, New Haven, Connecticut 06520, United States

Panluminate, Inc. New Haven, Connecticut 06516, United States

Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73126, United States

Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, Connecticut 06510, United States

Department of Physics, Yale University, New Haven, Connecticut 06511, United States

Institute for Biomedical Engineering, Science, and Technology (IBEST), Norman, Oklahoma 73019, United States

Stephenson Cancer Center, Oklahoma City, Oklahoma 73104, United States

Funding

National Institute of Diabetes and Digestive and Kidney Diseases · Oklahoma Medical Research Foundation · Wellcome Trust · Oklahoma Center for the Advancement of Science and Technology · Division of Chemical, Bioengineering, Environmental, and Transport Systems · National Institute of General Medical Sciences

References (68)

Show source-provided references
1. 10.3389/fphar.2018.0079010.3389/fphar.2018.00790 ↗
2. 10.1038/cr.2010.1910.1038/cr.2010.19 ↗
3. 10.1038/s41565-021-00858-810.1038/s41565-021-00858-8 ↗
4. 10.3390/ijms22231278910.3390/ijms222312789 ↗
5. 10.1016/j.micron.2022.10330410.1016/j.micron.2022.103304 ↗
6. 10.1523/JNEUROSCI.3994-06.200610.1523/JNEUROSCI.3994-06.2006 ↗
7. 10.1038/s41596-020-0313-910.1038/s41596-020-0313-9 ↗
8. 10.1016/j.jviromet.2013.06.01810.1016/j.jviromet.2013.06.018 ↗
9. 10.1021/acsnano.6b0187910.1021/acsnano.6b01879 ↗
10. 10.1021/jacs.7b0402210.1021/jacs.7b04022 ↗
11. 10.1021/acs.bioconjchem.6b0050010.1021/acs.bioconjchem.6b00500 ↗
12. 10.1021/acs.nanolett.9b0485310.1021/acs.nanolett.9b04853 ↗
13. 10.1126/science.257.5067.18910.1126/science.257.5067.189 ↗
14. 10.1242/jcs.08008510.1242/jcs.080085 ↗
15. 10.1126/science.126008810.1126/science.1260088 ↗
16. 10.1038/s41467-020-17523-810.1038/s41467-020-17523-8 ↗
17. 10.1039/D0CS01127D10.1039/D0CS01127D ↗
18. 10.1021/acsomega.0c0516210.1021/acsomega.0c05162 ↗
19. 10.1002/smll.20130288910.1002/smll.201302889 ↗
20. 10.3390/ijms2114484710.3390/ijms21144847 ↗
21. 10.1016/j.addr.2019.04.00810.1016/j.addr.2019.04.008 ↗
22. 10.1002/adpr.20220009810.1002/adpr.202200098 ↗
23. 10.1021/jacs.9b0589410.1021/jacs.9b05894 ↗
24. 10.1038/nbt.362510.1038/nbt.3625 ↗
25. 10.15252/embr.20184583610.15252/embr.201845836 ↗
26. 10.7554/eLife.7377510.7554/eLife.73775 ↗
27. 10.1038/nmeth.426110.1038/nmeth.4261 ↗
28. 10.1038/nbt.389210.1038/nbt.3892 ↗
29. 10.1021/acsnano.1c1101510.1021/acsnano.1c11015 ↗
30. 10.1101/2021.05.18.44362910.1101/2021.05.18.443629 ↗
31. 10.1002/adfm.20200736310.1002/adfm.202007363 ↗
32. 10.1002/cpcb.5610.1002/cpcb.56 ↗
33. 10.1080/00219266.2002.965584710.1080/00219266.2002.9655847 ↗
34. 10.1186/s11671-018-2728-610.1186/s11671-018-2728-6 ↗
35. 10.1021/nl052396o10.1021/nl052396o ↗
36. 10.1021/ja907069u10.1021/ja907069u ↗
37. 10.1021/acsanm.9b0254110.1021/acsanm.9b02541 ↗
38. 10.1007/s00216-023-04540-x10.1007/s00216-023-04540-x ↗
39. 10.1021/acs.nanolett.2c0222610.1021/acs.nanolett.2c02226 ↗
40. 10.1021/acs.nanolett.2c0034910.1021/acs.nanolett.2c00349 ↗
41. 10.1007/s13404-014-0143-z10.1007/s13404-014-0143-z ↗
42. 10.1088/2050-6120/ab736510.1088/2050-6120/ab7365 ↗
43. 10.1021/acsnano.1c0741810.1021/acsnano.1c07418 ↗
44. 10.1038/s41598-020-59146-510.1038/s41598-020-59146-5 ↗
45. 10.1021/acsnano.9b0138310.1021/acsnano.9b01383 ↗
46. 10.1002/smtd.20210027910.1002/smtd.202100279 ↗
47. 10.1021/acs.nanolett.8b0343410.1021/acs.nanolett.8b03434 ↗
48. 10.2147/IJN.S12930010.2147/IJN.S129300 ↗
49. 10.1016/j.cell.2005.12.03810.1016/j.cell.2005.12.038 ↗
50. 10.1073/pnas.97.2.68010.1073/pnas.97.2.680 ↗
51. 10.1016/j.mex.2022.10179610.1016/j.mex.2022.101796 ↗
52. 10.1007/978-1-0716-1538-6_1810.1007/978-1-0716-1538-6_18 ↗
53. 10.1080/10408444.2021.190338610.1080/10408444.2021.1903386 ↗
54. 10.1007/s00216-020-02783-610.1007/s00216-020-02783-6 ↗
55. 10.1021/acs.nanolett.2c0103710.1021/acs.nanolett.2c01037 ↗
56. 10.1021/acs.nanolett.1c0375210.1021/acs.nanolett.1c03752 ↗
57. 10.1038/s41598-019-48838-210.1038/s41598-019-48838-2 ↗
58. 10.1038/nmeth.f.38810.1038/nmeth.f.388 ↗
59. 10.1021/nn901227410.1021/nn9012274 ↗
60. 10.2147/IJN.S21099210.2147/IJN.S210992 ↗
61. 10.1007/s10953-018-0830-010.1007/s10953-018-0830-0 ↗
62. 10.1002/smll.20040009310.1002/smll.200400093 ↗
63. 10.1002/adma.20170370410.1002/adma.201703704 ↗
64. 10.1021/acsnano.8b0390010.1021/acsnano.8b03900 ↗
65. 10.1021/acsami.5b0934410.1021/acsami.5b09344 ↗
66. 10.1080/0191312070171918910.1080/01913120701719189 ↗
67. Kannan K. S. · Int. J. Stat. Syst. · 2015 · 10 · 231
68. 10.1109/TSMC.1979.431007610.1109/TSMC.1979.4310076 ↗