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Development of a highly-efficient erythrocyte-drug covalent conjugation platform and its use in treating thrombotic disorders

Cell Research volume 33, pages 887–890 (2023)Cite this article

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Dear Editor,

Red blood cells (RBCs) are the most abundant cells in the human body. RBCs have been widely investigated as in vivo drug delivery systems due to their unique biological properties.1 RBCs lack nuclei and circulate in blood vessels with a 120-day lifespan.2 Good biocompatibility and a large surface-to-volume ratio make RBCs ideal vesicles for carrying many drug molecules.3 Previous research has explored several methods for drug delivery using RBCs as well as RBC-inspired delivery systems.4 One approach utilizing RBCs for drug delivery involves using osmotic pressure to transiently open the cell membrane and encapsulate drugs for sustained release. However, this method can damage the cell membrane, thus limiting its efficacy for long-term treatments. Another approach is to attach drugs to the surface of RBCs using noncovalent linkages, such as antigen-antibody binding. However, the drugs may detach from the cell surface soon after entering the body, making it challenging to achieve long-lasting therapeutic effects. A third approach is to adsorb drugs onto the surface of RBCs, but this method is similarly limited by noncovalent bindings, causing the drugs to detach from the cells within minutes to hours.5,6,7 The goal of our study is to develop an efficient method to directly engineer natural RBCs for drug delivery.

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Fig. 1: Engineering RBCs with pro-uPA for dissolving thrombi.

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Acknowledgements

We appreciate the technical support from the Biomedical Research Core Facilities and Laboratory Animal Resources Center of Westlake University. We thank Guolin Yu at the Zhejiang Xiaoshan hospital for providing the human samples. This project was supported in part by grants from the National Natural Science Foundation of China (81973993) and Zhejiang Provincial Natural Science Foundation of China (LR20C070001).

Author information

Author notes

  1. These authors contributed equally: Yanjie Huang, Xiaoqian Nie, Xuewen Liu.

Authors and Affiliations

  1. School of Basic Medical Sciences, Fudan University, Shanghai, China

    Yanjie Huang, Xiaoqian Nie & Xuewen Liu

  2. Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China

    Yanjie Huang, Xiaoqian Nie, Xuewen Liu, Yuehua Liu & Xiaofei Gao

  3. Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China

    Yanjie Huang, Xiaoqian Nie, Xuewen Liu, Yuehua Liu & Xiaofei Gao

  4. Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China

    Yanjie Huang, Xiaoqian Nie, Xuewen Liu, Yuehua Liu & Xiaofei Gao

  5. College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China

    Yuehua Liu

  6. Westlake Therapeutics, Inc., Hangzhou, Zhejiang, China

    Huifei Yu

Authors
  1. Yanjie Huang
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  2. Xiaoqian Nie
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  3. Xuewen Liu
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  4. Yuehua Liu
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  5. Huifei Yu
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  6. Xiaofei Gao
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Contributions

X.G. conceived and supervised the projects; Y.H. and H.Y. performed most of the experiments; and X.N. and X.L. performed the in vivo and in vitro characterization experiments. All other experiments were performed by X.N., X.L. and Y.L. All data were analyzed by Y.H., X.N. and X.L. under the supervision of Y.L. All authors contributed to data interpretation. X.G. and Y.H. wrote the manuscript with input from all of the authors.

Corresponding author

Correspondence to Xiaofei Gao.

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Competing interests

X.G. is a shareholder of Westlake Therapeutics Co., Ltd. The remaining authors declare no competing interests.

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Huang, Y., Nie, X., Liu, X. et al. Development of a highly-efficient erythrocyte-drug covalent conjugation platform and its use in treating thrombotic disorders. Cell Res 33, 887–890 (2023). https://doi.org/10.1038/s41422-023-00868-2

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  • DOI: https://doi.org/10.1038/s41422-023-00868-2

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