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Ligand-switchable nanoparticles resembling viral surface for sequential drug delivery and improved oral insulin therapy

Author

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  • Tiantian Yang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Aohua Wang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Di Nie

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Weiwei Fan

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Xiaohe Jiang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Miaorong Yu

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Shiyan Guo

    (Chinese Academy of Sciences)

  • Chunliu Zhu

    (Chinese Academy of Sciences)

  • Gang Wei

    (Fudan University)

  • Yong Gan

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences
    National Institutes for Food and Drug Control)

Abstract

Mutual interference between surface ligands on multifunctional nanoparticles remains a significant obstacle to achieving optimal drug-delivery efficacy. Here, we develop ligand-switchable nanoparticles which resemble viral unique surfaces, enabling them to fully display diverse functions. The nanoparticles are modified with a pH-responsive stretchable cell-penetrating peptide (Pep) and a liver-targeting moiety (Gal) (Pep/Gal-PNPs). Once orally administered, the acidic environments trigger the extension of Pep from surface in a virus-like manner, enabling Pep/Gal-PNPs to traverse intestinal barriers efficiently. Subsequently, Gal is exposed by Pep folding at physiological pH, thereby allowing the specific targeting of Pep/Gal-PNPs to the liver. As a proof-of-concept, insulin-loaded Pep/Gal-PNPs are fabricated which exhibit effective intestinal absorption and excellent hepatic deposition of insulin. Crucially, Pep/Gal-PNPs increase hepatic glycogen production by 7.2-fold, contributing to the maintenance of glucose homeostasis for effective diabetes management. Overall, this study provides a promising approach to achieving full potential of diverse ligands on multifunctional nanoparticles.

Suggested Citation

  • Tiantian Yang & Aohua Wang & Di Nie & Weiwei Fan & Xiaohe Jiang & Miaorong Yu & Shiyan Guo & Chunliu Zhu & Gang Wei & Yong Gan, 2022. "Ligand-switchable nanoparticles resembling viral surface for sequential drug delivery and improved oral insulin therapy," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34357-8
    DOI: 10.1038/s41467-022-34357-8
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    References listed on IDEAS

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