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

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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Figure 1: Mesoporous-silica–coated NaYF4:Yb,Er UCN as an agent of PDT.
Figure 2: Dual photosensitizer approach with single-wavelength activation using UCNs for enhanced PDT.
Figure 3: In vivo PDT of injected tumor cells prelabeled with UCN.
Figure 4: In vivo PDT of a subcutaneous tumor model injected with UCNs.
Figure 5: Targeted in vivo PDT of a subcutaneous tumor model injected with FA-PEG-UCNs.

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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.

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Authors and Affiliations

Authors

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.

Corresponding author

Correspondence to Yong Zhang.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–6 and Supplementary Methods (PDF 339 kb)

Supplementary Video 1

Rotation of a volume rendered z-stacks of the green upconversion fluorescence of a suspended UCN-labeled cell. (MOV 2161 kb)

Supplementary Video 2

Rotation of a volume rendered z-stacks of the DAPI-stained nucleus of a suspended UCN-labeled cell. (MOV 519 kb)

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Idris, N., Gnanasammandhan, M., Zhang, J. et al. In vivo photodynamic therapy using upconversion nanoparticles as remote-controlled nanotransducers. Nat Med 18, 1580–1585 (2012). https://doi.org/10.1038/nm.2933

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