Barcoded screening identifies nanocarriers for protein delivery to kidney

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 design...

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Main Authors: 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
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-56257-3
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author 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
author_facet 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
author_sort Luyao Wang
collection DOAJ
description 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.
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institution Kabale University
issn 2041-1723
language English
publishDate 2025-01-01
publisher Nature Portfolio
record_format Article
series Nature Communications
spelling doaj-art-7f3b6be807894580b29e7bb2b850a63a2025-01-26T12:42:07ZengNature PortfolioNature Communications2041-17232025-01-0116111510.1038/s41467-025-56257-3Barcoded screening identifies nanocarriers for protein delivery to kidneyLuyao Wang0Wen Zhou1Hang Chen2Xiangqian Jia3Peiyuan Zheng4Haolin Jiang5Mengling Wu6Yaning Zhang7Yanchao Ding8Yexi Peng9Rui Zhu10Tiantian Li11Boxue Tian12Bujie Du13Juanjuan Du14School of Pharmaceutical Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua UniversitySchool of Pharmaceutical Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua UniversitySchool of Pharmaceutical Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua UniversitySchool of Pharmaceutical Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua UniversitySchool of Pharmaceutical Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua UniversitySchool of Pharmaceutical Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua UniversitySchool of Pharmaceutical Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua UniversitySchool of Pharmaceutical Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua UniversitySchool of Pharmaceutical Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua UniversityCenter for Medical Research on Innovation and Translation, Institute of Clinical Medicine, The Second Affiliated Hospital, School of Medicine, South China University of TechnologySchool of Pharmaceutical Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua UniversitySchool of Pharmaceutical Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua UniversitySchool of Pharmaceutical Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua UniversityCenter for Medical Research on Innovation and Translation, Institute of Clinical Medicine, The Second Affiliated Hospital, School of Medicine, South China University of TechnologySchool of Pharmaceutical Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua UniversityAbstract 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.https://doi.org/10.1038/s41467-025-56257-3
spellingShingle 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
Barcoded screening identifies nanocarriers for protein delivery to kidney
Nature Communications
title Barcoded screening identifies nanocarriers for protein delivery to kidney
title_full Barcoded screening identifies nanocarriers for protein delivery to kidney
title_fullStr Barcoded screening identifies nanocarriers for protein delivery to kidney
title_full_unstemmed Barcoded screening identifies nanocarriers for protein delivery to kidney
title_short Barcoded screening identifies nanocarriers for protein delivery to kidney
title_sort barcoded screening identifies nanocarriers for protein delivery to kidney
url https://doi.org/10.1038/s41467-025-56257-3
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