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Barcoded screening identifies nanocarriers for protein delivery to kidney

Author

Listed:
  • Luyao Wang

    (Tsinghua University)

  • Wen Zhou

    (Tsinghua University)

  • Hang Chen

    (Tsinghua University)

  • Xiangqian Jia

    (Tsinghua University)

  • Peiyuan Zheng

    (Tsinghua University)

  • Haolin Jiang

    (Tsinghua University
    Peking University)

  • Mengling Wu

    (Tsinghua University)

  • Yaning Zhang

    (Tsinghua University
    Tsinghua University)

  • Yanchao Ding

    (Tsinghua University)

  • Yexi Peng

    (South China University of Technology)

  • Rui Zhu

    (Tsinghua University)

  • Tiantian Li

    (Tsinghua University)

  • Boxue Tian

    (Tsinghua University)

  • Bujie Du

    (South China University of Technology)

  • Juanjuan Du

    (Tsinghua University)

Abstract

Targeted protein delivery with nanocarriers holds significant potential to enhance therapeutic outcomes by precisely directing proteins to specific organs or tissues. However, the complex interactions between nanocarriers and the biological environment pose considerable challenges in designing effective targeted delivery vehicles. In this study, we address this challenge by leveraging DNA-barcoded high-throughput screening. We construct a nanocapsule library via in-situ polymerization, incorporating various monomers to create nanocapsules with unique surface properties. In vitro and in vivo screening, using female mice, identify nanocapsules with high cell association and different biodistribution. Our investigation into kidney-enriched nanocapsules highlights the crucial role of polymer composition in biodistribution, demonstrating the potential of surface engineering for precise control over nanoparticle distribution. The kidney-enriched nanocapsule successfully delivers catalase, showcasing its therapeutic potential in mitigating cisplatin-induced acute kidney injury. Overall, our study presents an approach for identifying protein delivery vehicles, with the capacity to broaden the application of proteins as therapeutic agents or research tools.

Suggested Citation

  • Luyao Wang & Wen Zhou & Hang Chen & Xiangqian Jia & Peiyuan Zheng & Haolin Jiang & Mengling Wu & Yaning Zhang & Yanchao Ding & Yexi Peng & Rui Zhu & Tiantian Li & Boxue Tian & Bujie Du & Juanjuan Du, 2025. "Barcoded screening identifies nanocarriers for protein delivery to kidney," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56257-3
    DOI: 10.1038/s41467-025-56257-3
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    References listed on IDEAS

    as
    1. Joseph Kreitz & Mirco J. Friedrich & Akash Guru & Blake Lash & Makoto Saito & Rhiannon K. Macrae & Feng Zhang, 2023. "Programmable protein delivery with a bacterial contractile injection system," Nature, Nature, vol. 616(7956), pages 357-364, April.
    2. Sasha B. Ebrahimi & Devleena Samanta, 2023. "Engineering protein-based therapeutics through structural and chemical design," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    3. Tuo Wei & Qiang Cheng & Yi-Li Min & Eric N. Olson & Daniel J. Siegwart, 2020. "Systemic nanoparticle delivery of CRISPR-Cas9 ribonucleoproteins for effective tissue specific genome editing," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
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