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A novel intracellular protein delivery platform based on single-protein nanocapsules

Nature Nanotechnology volume 5, pages 4853 (2010) | Download Citation

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Abstract

An average cell contains thousands of proteins that participate in normal cellular functions, and most diseases are somehow related to the malfunctioning of one or more of these proteins. Protein therapy1, which delivers proteins into the cell to replace the dysfunctional protein, is considered the most direct and safe approach for treating disease. However, the effectiveness of this method has been limited by its low delivery efficiency and poor stability against proteases in the cell, which digest the protein. Here, we show a novel delivery platform based on nanocapsules consisting of a protein core and a thin permeable polymeric shell that can be engineered to either degrade or remain stable at different pHs. Non-degradable capsules show long-term stability, whereas the degradable ones break down their shells, enabling the core protein to be active once inside the cells. Multiple proteins can be delivered to cells with high efficiency while maintaining low toxicity, suggesting potential applications in imaging, therapy and cosmetics fields.

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Acknowledgements

This work was partially supported by the Defense Threat Reducing Agency (DTRA), NSF-CAREER, Sandia National Laboratories and CheungKong Scholar Program through Tsinghua University, China.

Author information

Author notes

    • Ming Yan
    •  & Juanjuan Du

    These authors contributed equally to this work

Affiliations

  1. Department of Chemical and Biomolecular Engineering, University of California at Los Angeles, Los Angeles, California 90095, USA

    • Ming Yan
    • , Juanjuan Du
    • , Zhen Gu
    • , Wenjun Zhang
    • , Tatiana Segura
    • , Yi Tang
    •  & Yunfeng Lu
  2. Department of Microbiology, Immunology and Molecular Genetics, University of California at Los Angeles, Los Angeles, California 90095, USA

    • Min Liang
    •  & Z. Hong Zhou
  3. Department of Medical and Molecular Pharmacology, UCLA David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90095, USA

    • Yufang Hu
    • , Saul Priceman
    •  & Lily Wu
  4. California NanoSystems Institute, University of California at Los Angeles, Los Angeles, California 90095, USA

    • Z. Hong Zhou
  5. Department of Chemical Engineering, Tsinghua University, Beijing 10084, China

    • Zheng Liu

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Contributions

M.Y., Z.L., T.S., Y.T. and Y.L. conceived and designed the experiments. M.Y., J.D. and Z.G. performed the experiments. Y.H., W.Z., L.W. and Z.H.Z. helped to analyse the data. Z.L., T.S., Y.T. and Y.L. co-wrote the paper. All authors discussed the results and commented on the manuscript.

Corresponding authors

Correspondence to Zheng Liu or Tatiana Segura or Yi Tang or Yunfeng Lu.

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DOI

https://doi.org/10.1038/nnano.2009.341

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