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<p>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.</p>

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Designable synthetic complex coacervates enabling protein delivery to cells

  • 期刊论文

  • 发表日期：

    2025年5月9日

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  • Bing Jhang Li,
  • Biplab K C,
  • Teruki Nii,
  • Takeshi Mori,
  • Yoshiki Katayama,
  • Akihiro Kishimura

摘要

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.