Truly Tiny Acoustic Biomolecules for Ultrasound Imaging and Therapy
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1.
California Institute of Technology
Abstract
Nanotechnology offers significant advantages for medical imaging and therapy, including enhanced contrast and precision targeting. However, integrating these benefits into ultrasonography is challenging due to the size and stability constraints of conventional bubble-based agents. Here bicones, truly tiny acoustic contrast agents based on gas vesicles (GVs), a unique class of air-filled protein nanostructures naturally produced in buoyant microbes, are described. It is shown that these sub-80 nm particles can be effectively detected both in vitro and in vivo, infiltrate tumors via leaky vasculature, deliver potent mechanical effects through ultrasound-induced inertial cavitation, and are easily engineered for molecular targeting, prolonged circulation time, and payload conjugation.
Copyright and License
© 2024 The Authors. Advanced Materials published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Acknowledgement
The authors thank Dr. Andres Collazo and the Caltech Biological Imaging Facility of the Beckman Institute for assistance with confocal microscopy; Dr. Songye Chen and the Caltech Cryo-EM facility for assistance with cryo-EM and TEM; Dr. Lena Gamboa for assistance with IVIS imaging; Dr. Di Wu, Dr. Avinoam Bar-Zion, Dr. Constantine Sideris, and Dr. George Lu for helpful discussions. Parts of Figure 6 were created with BioRender. This research was supported by the National Institutes of Health (grant R01-EB018975 to M.G.S.). M.G.S. is a Howard Hughes Medical Institute Investigator.
Contributions
B.L. and M.G.S. conceptualized the research. B.L., B.G., and R.V. prepared and characterized all bicone variants. P.D. conducted cryo-EM experiments. B.L., Y.Y., R.V., R.N., and C.A.B.S. conducted the cavitation experiments. B.L. and J.L conducted flow cytometry experiments. B.L. conducted in vivo experiments with assistance from M.B.S. B.L. and M.G.S. wrote the manuscript with input from all other authors. M.G.S. supervised the research.
Data Availability
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Conflict of Interest
The authors declare no conflict of interest.
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Additional details
- ISSN
- 1521-4095
- National Institutes of Health
- R01‐EB018975
- Howard Hughes Medical Institute
- Caltech groups
- Tianqiao and Chrissy Chen Institute for Neuroscience, Richard N. Merkin Institute for Translational Research