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A multifunctional core–shell nanoparticle for dendritic cell-based cancer immunotherapy

Nature Nanotechnology volume 6, pages 675–682 (2011)Cite this article

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Abstract

Dendritic cell-based cancer immunotherapy requires tumour antigens to be delivered efficiently into dendritic cells and their migration to be monitored in vivo. Nanoparticles have been explored as carriers for antigen delivery, but applications have been limited by the toxicity of the solvents used to make nanoparticles, and by the need to use transfection agents to deliver nanoparticles into cells. Here we show that an iron oxide–zinc oxide core–shell nanoparticle can deliver carcinoembryonic antigen into dendritic cells while simultaneously acting as an imaging agent. The nanoparticle–antigen complex is efficiently taken up by dendritic cells within one hour and can be detected in vitro by confocal microscopy and in vivo by magnetic resonance imaging. Mice immunized with dendritic cells containing the nanoparticle–antigen complex showed enhanced tumour antigen specific T-cell responses, delayed tumour growth and better survival than controls.

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Figure 1: Characterization of the Fe3O4–ZnO core–shell nanoparticle.
Figure 2: Immobilization of polypeptide on the nanoparticle.
Figure 3: Intracellular delivery of the nanoparticles into DCs.
Figure 4: In vitro and in vivo MRI of nanoparticle-labelled DCs.
Figure 5: Induction of CEA-specific immunity.
Figure 6: Tumour growth and survival of immunized mice.

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Acknowledgements

This work was supported by the Pioneer Research Center Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (2011-0001715). Y.K.K. was supported by the Leap Research Program through the National Research Foundation of Korea (2011-0016497) and the Industrial Core Technology Development Program funded by the Ministry of Knowledge Economy (10033183). S.Y.S. and N.H.C. were supported by a grant from the Innovative Research Institute of Cell Therapy funded by the Ministry of Health and Welfare (A062260). T.C.C. and J.H.M. were supported by Hi Seoul Science/Humanities Fellowship from Seoul Scholarship Foundation. The authors are grateful to N. Orazio for critical reading of the manuscript.

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Author notes

  1. Nam-Hyuk Cho, Taek-Chin Cheong, Ji Hyun Min and Jun Hua Wu: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Microbiology and Immunology, Seoul National University College of Medicine and Institute of Endemic Diseases, Seoul National University Medical Research Center, Seoul, Republic of Korea

    Nam-Hyuk Cho, Taek-Chin Cheong & Seung-Yong Seong

  2. Department of Biomedical Sciences, Seoul National University College of Medicine and Institute of Endemic Diseases, Seoul National University Medical Research Center, Seoul, Republic of Korea

    Nam-Hyuk Cho, Taek-Chin Cheong & Seung-Yong Seong

  3. Bundang Hospital, Seoul, Republic of Korea

    Nam-Hyuk Cho

  4. Research Institute, National Cancer Center, Goyang, Gyeonggi-do, Republic of Korea

    Taek-Chin Cheong, Sang Jin Lee & Daehong Kim

  5. Department of Materials Science and Engineering, Korea University, Seoul, Republic of Korea

    Ji Hyun Min & Young Keun Kim

  6. Pioneer Research Center for Biomedical Nanocrystals, Korea University, Seoul, Republic of Korea

    Ji Hyun Min, Jun Hua Wu, Young Keun Kim & Seung-Yong Seong

  7. Department of Life Science and School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, Gyungbuk, Republic of Korea

    Jae-Seong Yang & Sanguk Kim

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Contributions

N-H.C., S-Y.S. and Y.K.K. conceived and designed the experiments. T-C.C., J.H.M., J.H.W., S.J.L., D.H.K., J-S.Y. and S.K. performed the experiments. N-H.C., S-Y.S. and Y.K.K. analysed the data and wrote the paper. All authors discussed the results and commented on the manuscript.

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Correspondence to Young Keun Kim or Seung-Yong Seong.

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Cho, NH., Cheong, TC., Min, J. et al. A multifunctional core–shell nanoparticle for dendritic cell-based cancer immunotherapy. Nature Nanotech 6, 675–682 (2011). https://doi.org/10.1038/nnano.2011.149

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