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In situ conversion of porphyrin microbubbles to nanoparticles for multimodality imaging

Nature Nanotechnology volume 10, pages 325–332 (2015)Cite this article

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Abstract

Converting nanoparticles or monomeric compounds into larger supramolecular structures by endogenous1,2 or external3,4 stimuli is increasingly popular because these materials are useful for imaging and treating diseases. However, conversion of microstructures to nanostructures is less common. Here, we show the conversion of microbubbles to nanoparticles using low-frequency ultrasound. The microbubble consists of a bacteriochlorophyll–lipid shell around a perfluoropropane gas. The encapsulated gas provides ultrasound imaging contrast and the porphyrins in the shell confer photoacoustic and fluorescent properties. On exposure to ultrasound, the microbubbles burst and form smaller nanoparticles that possess the same optical properties as the original microbubble. We show that this conversion is possible in tumour-bearing mice and could be validated using photoacoustic imaging. With this conversion, our microbubble can potentially be used to bypass the enhanced permeability and retention effect when delivering drugs to tumours.

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Figure 1: Schematics of porphyrin microbubbles (pMBs) and their micro-to-nano conversion.
Figure 2: Characterization of the conversion of pMBs to pNPs.
Figure 3: Optical spectra of pMBs and resulting pNPs after interaction with conversion ultrasound.
Figure 4: Multimodal imaging of pMBs and resulting pNPs following ultrasound-induced conversion.
Figure 5: Conversion of pMBs to pNPs in vivo in mice.

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Acknowledgements

The authors thank A. Roxin for providing the BChl-lipid, P. McVeigh for technical assistance with the NanoSight LM10, M. Balassu for technical assistance with the animal study and D.M. Charron for help with electron microscopy. The authors also thank R-K. Li for use of his Vevo SoniGene instrument. This work was supported by the Canadian Institutes of Health Research (CIHR) Frederick Banting and Charles Best Canada Graduate Scholarship, the Emerging Team Grant on Regenerative Medicine and Nanomedicine co-funded by the CIHR and the Canadian Space Agency, the Natural Sciences and Engineering Research Council of Canada, the Ontario Institute for Cancer Research, the International Collaborative R&D Project of the Ministry of Knowledge Economy, South Korea, the Joey and Toby Tanenbaum/Brazilian Ball Chair in Prostate Cancer Research, the Canada Foundation for Innovation and the Princess Margaret Cancer Foundation.

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Authors and Affiliations

  1. Princess Margaret Cancer Center and Techna Institute, University Health Network, Toronto, M5G 2M9, Ontario, Canada

    Elizabeth Huynh, Mojdeh Shakiba, Cheng S. Jin, Brian C. Wilson & Gang Zheng

  2. Department of Medical Biophysics, University of Toronto, Toronto, M5G 1L7, Ontario, Canada

    Elizabeth Huynh, Brandon L. Helfield, Mojdeh Shakiba, Brian C. Wilson, David E. Goertz & Gang Zheng

  3. Sunnybrook Health Sciences Center, Toronto, M4N 3M5, Ontario, Canada

    Ben Y. C. Leung, Brandon L. Helfield & David E. Goertz

  4. Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, M5S 3E5, Ontario, Canada

    Julie-Anne Gandier & Emma R. Master

  5. Department of Pharmaceutical Sciences, University of Toronto, Toronto, M5S 3M2, Ontario, Canada

    Cheng S. Jin & Gang Zheng

  6. Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, M5G 1L7, Ontario, Canada

    Cheng S. Jin & Gang Zheng

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  1. Elizabeth Huynh
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Contributions

E.H. and G.Z. conceived the idea, interpreted the data and wrote the manuscript. E.H., D.E.G. and G.Z. designed the experiments. E.H. carried out size characterization, light microscopy, optical characterization and imaging studies. B.Y.C.L., B.L.H. and E.H. performed acoustic characterization. M.S. and E.H. carried out electron microscopy. E.H. and C.S.J. carried out animal imaging experiments. J.G. and E.R.M. carried out flow field-flow fractionation. E.H., D.E.G., B.C.W. and G.Z. edited the manuscript.

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Correspondence to Gang Zheng.

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The authors declare no competing financial interests.

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Huynh, E., Leung, B., Helfield, B. et al. In situ conversion of porphyrin microbubbles to nanoparticles for multimodality imaging. Nature Nanotech 10, 325–332 (2015). https://doi.org/10.1038/nnano.2015.25

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