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Designable synthetic complex coacervates enabling protein delivery to cells

Polymer Journal volume 57, pages 911–922 (2025)Cite this article

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Abstract

Biomolecular condensates offer a versatile platform for the accumulation of biomacromolecules, particularly proteins. This study investigated synthetic complex coacervates as a model of biomolecular condensates and developed a novel tool for the intracellular delivery of proteins to overcome the issues of cytotoxicity and poor cellular uptake. By optimizing preparation conditions and chemical structures and developing a simple pre-coating method, we achieved an improvement in the interaction and internalization of coacervates for HeLa and Jurkat cells and the reduction of cytotoxicity. Furthermore, the use of charge-density reduced polymers enabled the effective encapsulation and intracellular delivery of various proteins. The mechanism of cellular internalization was also investigated, and macropinocytosis was concluded to be a primary internalization pathway. These findings provide a foundation for future advancements in biomaterials.

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Acknowledgements

This research was supported in part by JSPS KAKENHI (JP24H01151, JP23K23469, and 22H05429 to AK). BJL is grateful to the “Future-Creation (MIRAI)” Course, Kyushu University SPRING program (No. JPMJSP2136) for scholarship and research fund. We thank Drs. M. Goto, N. Kamiya, and R. Wakabayashi (Kyushu University) for their assistance with the CLSM measurements. We would like to thank Editage (www.editage.jp) for English language editing.

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Authors and Affiliations

  1. Graduate School of System Life Sciences, Kyushu University, 744 Moto-oka, Nishi-ku, Fukuoka, 819-0395, Japan

    Bing Jhang Li & Biplab K C

  2. Department of Applied Chemistry, Faculty of Engineering, Kyushu University, 744 Moto-oka, Nishi-Ku, Fukuoka, 819-0395, Japan

    Biplab K C, Teruki Nii, Takeshi Mori, Yoshiki Katayama & Akihiro Kishimura

  3. Center for Future Chemistry (CFC), Kyushu University, 744 Moto-oka, Nishi-Ku, Fukuoka, 819-0395, Japan

    Takeshi Mori, Yoshiki Katayama & Akihiro Kishimura

  4. Center of Molecular Systems (CMS), Kyushu University, 744 Moto-oka, Nishi-Ku, Fukuoka, 819-0395, Japan

    Yoshiki Katayama & Akihiro Kishimura

  5. Center of Advanced Medical Open Innovation, Kyushu University, 3-1-1 Maidashi,Higashi-ku, Fukuoka, 812-8582, Japan

    Yoshiki Katayama

  6. Department of Biomedical Engineering, Chung Yuan Christian University, 200 Chung Pei Rd., Chung Li, 32023, Taiwan, ROC

    Yoshiki Katayama

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  1. Bing Jhang Li
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  2. Biplab K C
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  6. Akihiro Kishimura
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Contributions

BJL performed the experiments and prepared the manuscript. BKC gave advice on the experiments. AK designed the research as a supervisor of BJL, validated data, and prepared the manuscript. TN, TM, and YK also validated data and gave advice on the experiments and manuscript preparation.

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Correspondence to Akihiro Kishimura.

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Li, B.J., K C, B., Nii, T. et al. Designable synthetic complex coacervates enabling protein delivery to cells. Polym J 57, 911–922 (2025). https://doi.org/10.1038/s41428-025-01043-7

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