Rapid translocation of nanoparticles from the lung airspaces to the body

Abstract

Nano-size particles show promise for pulmonary drug delivery, yet their behavior after deposition in the lung remains poorly understood. In this study, a series of near-infrared (NIR) fluorescent nanoparticles were systematically varied in chemical composition, shape, size and surface charge, and their biodistribution and elimination were quantified in rat models after lung instillation. We demonstrate that nanoparticles with hydrodynamic diameter (HD) less than ≈34 nm and a noncationic surface charge translocate rapidly from the lung to mediastinal lymph nodes. Nanoparticles of HD < 6 nm can traffic rapidly from the lungs to lymph nodes and the bloodstream, and then be subsequently cleared by the kidneys. We discuss the importance of these findings for drug delivery, air pollution and carcinogenesis.

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Figure 1: Schematic structures of inorganic/organic hybrid nanoparticles (INPs, 800 nm emission) and organic nanoparticles (ONPs, 700 nm emission) and their size- and charge-dependent translocation.
Figure 2: Biodistribution, clearance and histological analysis of INPs in Sprague-Dawley rats.

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Acknowledgements

We thank R. Oketokoun and S. Gioux for help with developing the FLARE imaging system and E.P. Lunsford of the Longwood Small Animal Imaging Facility for assistance with SPECT/CT imaging. The Biophysical Instrumentation Facility for the Study of Complex Macromolecular Systems (National Science Foundation-0070319 and US National Institutes of Health (NIH) GM68762) is gratefully acknowledged. We thank W. Liu and B.I. Ipe for providing quantum dots, L. Moffitt for editing, and L. Keys and E. Trabucchi for administrative support. This work was supported in part by NIH grant HL054885 (A.T.), HL070542 (A.T.), HL074022 (A.T.) and R01-CA-115296 (J.V.F.).

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Contributions

H.S.C., Y.A., J.H.L., S.H.K., A.M., N.I. and A.T. performed the experiments. H.S.C., M.G.B., M.S.-B., A.T. and J.V.F. reviewed, analyzed and interpreted the data. H.S.C., A.T. and J.V.F. wrote the paper. All authors discussed the results and commented on the manuscript.

Corresponding authors

Correspondence to John V Frangioni or Akira Tsuda.

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Competing interests

All FLARE technology is owned by Beth Israel Deaconess Medical Center, a teaching hospital of Harvard Medical School. As inventor, Dr. Frangioni may someday receive royalties if products are commercialized. Dr. Frangioni is the founder and unpaid director of The FLARE Foundation, a non-profit organization focused on promoting the dissemination of medical imaging technology for research and clinical use.

Supplementary information

Supplementary Text and Figures

Supplementary Figs. 1–6 (PDF 1442 kb)

Supplementary Video 1

Real-Time Translocation of NPs from the Lung to a Mediastinal Lymph Node (ZIP 1332 kb)

Supplementary Video 2

Real-Time Clearance of NPs from Kidneys to Bladder (ZIP 3585 kb)

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Choi, H., Ashitate, Y., Lee, J. et al. Rapid translocation of nanoparticles from the lung airspaces to the body. Nat Biotechnol 28, 1300–1303 (2010). https://doi.org/10.1038/nbt.1696

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