Technical Report | Published:

In vivo photodynamic therapy using upconversion nanoparticles as remote-controlled nanotransducers

Nature Medicine volume 18, pages 15801585 (2012) | Download Citation

Abstract

Conventional photodynamic therapy (PDT) is limited by the penetration depth of visible light needed for its activation. Here we used mesoporous-silica–coated upconversion fluorescent nanoparticles (UCNs) as a nanotransducer to convert deeply penetrating near-infrared light to visible wavelengths and a carrier of photosensitizers. We also used the multicolor-emission capability of the UCNs at a single excitation wavelength for simultaneous activation of two photosensitizers for enhanced PDT. We showed a greater PDT efficacy with the dual-photosensitizer approach compared to approaches using a single photosensitizer, as determined by enhanced generation of singlet oxygen and reduced cell viability. In vivo studies also showed tumor growth inhibition in PDT-treated mice by direct injection of UCNs into melanoma tumors or intravenous injection of UCNs conjugated with a tumor-targeting agent into tumor-bearing mice. As the first demonstration, to the best of our knowledge, of the photosensitizer-loaded UCN as an in vivo–targeted PDT agent, this finding may serve as a platform for future noninvasive deep-cancer therapy.

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Acknowledgements

We thank Z.Q. Li, A. Priyam and C.X. Li (Department of Bioengineering, Faculty of Engineering, National University of Singapore) for synthesis of the nanoparticles and S. Rajan for technical support in preparing the schematic illustration. We also acknowledge financial support from the Agency for Science, Technology and Research (A*STAR) Biomedical Research Council (grants R-397-000-062-305 and R-397-000-119-305) and National University of Singapore.

Author information

Affiliations

  1. Department of Bioengineering, Faculty of Engineering, National University of Singapore, Singapore.

    • Niagara Muhammad Idris
    • , Muthu Kumara Gnanasammandhan
    •  & Yong Zhang
  2. Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore.

    • Jing Zhang
    •  & Paul C Ho
  3. Department of Surgery, Faculty of Medicine, National University of Singapore, Singapore.

    • Ratha Mahendran
  4. Nanoscience and Nanotechnology Initiative, National University of Singapore, Singapore.

    • Yong Zhang
  5. National University of Singapore (NUS) Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore.

    • Yong Zhang

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Contributions

N.M.I. and Y.Z. conceived of and designed the experiments, analyzed the data and wrote the paper. N.M.I. performed most of the experiments, and M.K.G. performed the targeted PDT experiments. J.Z., P.C.H. and R.M. contributed to the data analyses and discussion.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Yong Zhang.

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1–6 and Supplementary Methods

Videos

  1. 1.

    Supplementary Video 1

    Rotation of a volume rendered z-stacks of the green upconversion fluorescence of a suspended UCN-labeled cell.

  2. 2.

    Supplementary Video 2

    Rotation of a volume rendered z-stacks of the DAPI-stained nucleus of a suspended UCN-labeled cell.

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DOI

https://doi.org/10.1038/nm.2933

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