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Porphysome nanovesicles generated by porphyrin bilayers for use as multimodal biophotonic contrast agents

Nature Materials volume 10, pages 324–332 (2011)Cite this article

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Abstract

Optically active nanomaterials promise to advance a range of biophotonic techniques through nanoscale optical effects and integration of multiple imaging and therapeutic modalities. Here, we report the development of porphysomes; nanovesicles formed from self-assembled porphyrin bilayers that generated large, tunable extinction coefficients, structure-dependent fluorescence self-quenching and unique photothermal and photoacoustic properties. Porphysomes enabled the sensitive visualization of lymphatic systems using photoacoustic tomography. Near-infrared fluorescence generation could be restored on dissociation, creating opportunities for low-background fluorescence imaging. As a result of their organic nature, porphysomes were enzymatically biodegradable and induced minimal acute toxicity in mice with intravenous doses of 1,000 mg kg−1. In a similar manner to liposomes, the large aqueous core of porphysomes could be passively or actively loaded. Following systemic administration, porphysomes accumulated in tumours of xenograft-bearing mice and laser irradiation induced photothermal tumour ablation. The optical properties and biocompatibility of porphysomes demonstrate the multimodal potential of organic nanoparticles for biophotonic imaging and therapy.

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Figure 1: Porphysomes are optically active nanovesicles formed from porphyrin bilayers.
Figure 2: Porphysomes demonstrate extensive and structurally driven self-quenching.
Figure 3: Multimodal optical utility of porphysomes.
Figure 4: Porphysomes are enzymatically biodegradable and well tolerated in vivo.
Figure 5: Active and passive loading of porphysomes.
Figure 6: Porphysomes as photothermal therapy agents.

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Acknowledgements

We thank B. G. Neel for editing, B. C. Wilson and C. M. Yip for insightful discussion, P. V. Turner for histopathology analysis, and E. Kumacheva and L. Tzadu for providing gold nanorods. This work was supported by grants from the Ontario Institute for Cancer Research, the Canadian Cancer Society, the Natural Sciences and Engineering Research Council of Canada, the Canadian Institute of Health Research, the Canadian Foundation of Innovation, the Joey and Toby Tanenbaum/Brazilian Ball Chair in Prostate Cancer Research, and in part from the Campbell Family Institute for Cancer Research, the Princess Margaret Hospital Foundation and the Ministry of Health and Long-Term Planning.

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Authors and Affiliations

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

    Jonathan F. Lovell, Cheng S. Jin, Warren C. W. Chan & Gang Zheng

  2. Ontario Cancer Institute, University Health Network, Ontario M5G 1L7, Canada

    Jonathan F. Lovell, Cheng S. Jin, Elizabeth Huynh, Honglin Jin & Gang Zheng

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

    Elizabeth Huynh, Honglin Jin, John L. Rubinstein & Gang Zheng

  4. Department of Biomedical Engineering, Optical Imaging Lab, Washington University in St Louis, Missouri 63130, USA

    Chulhong Kim & Lihong V. Wang

  5. Hospital for Sick Children Research Institute, Ontario M5G 1X8, Canada

    John L. Rubinstein

  6. Department of Chemistry, Shanghai University, Shanghai 200444, China

    Weiguo Cao

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  1. Jonathan F. Lovell
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Contributions

J.F.L. and G.Z. conceived the project, interpreted the data and wrote the manuscript. J.F.L., W.C.W.C. and G.Z. planned the experiments. C.S.J. and J.F.L. carried out photothermal tumour ablation. C.S.J. carried out confocal microscopy. E.H. and J.F.L. carried out most porphysome formation, photophysical characterization and drug encapsulation. H.J. and J.F.L. carried out toxicity experiments. J.L.R. carried out electron microscopy. C.K and L.V.W. carried out the photoacoustic experiments. W.C. and J.F.L. prepared the porphysome starting materials.

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Correspondence to Jonathan F. Lovell or Gang Zheng.

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Lovell, J., Jin, C., Huynh, E. et al. Porphysome nanovesicles generated by porphyrin bilayers for use as multimodal biophotonic contrast agents. Nature Mater 10, 324–332 (2011). https://doi.org/10.1038/nmat2986

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