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<p>The leverage of synthetic polymer self-assemblies (SPSAs) as biomimetic allostery provides unique opportunities for developing bio-inspired soft species. However, the preparation of these soft species remains a challenge likely due to the synthetic difficulties toward SPSAs having four-level hierarchical structural transitions and the compromised colloidal stability of the self-assembled quaternary structures. Herein, we report self-assembly of topological polymers with hydrophilic multicycles (HMCs) for biomimetic allostery. Specifically, cationic copolymers containing HMCs are prepared via a reliable synthetic approach, whose hierarchical self-assembly affords stabilized nanoparticles that undergo biomimetic allostery into quaternary petalled self-assemblies at an intracellular acidic pH of 5.0. The quaternary petalled self-assemblies lead to a mechanical disruption effect on lysosomes like nanomachines, further resulting in enhanced drug delivery efficiency of an anticancer drug-loaded multicyclic copolymers with a tumor inhibition rate 1.6-fold greater than that of the free drug in a murine 4T1 model. Overall, our work highlights the use of HMCs as biomimetic allostery of SPSAs for enhanced biomedical applications.</p>

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Harnessing multicyclic topologies as biomimetic allostery with mechanical lysosome disruption properties for enhanced drug delivery

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月3日

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  • Wei Ma,
  • Jin-Yan Zhang,
  • Dun Wang,
  • Zhi-Cheng Li,
  • Xiang-Yi Cheng,
  • Ling-Long Chen,
  • Ying Liu,
  • Gui-Ying Kang,
  • Cui-Yun Yu,
  • Hua Wei

摘要

The leverage of synthetic polymer self-assemblies (SPSAs) as biomimetic allostery provides unique opportunities for developing bio-inspired soft species. However, the preparation of these soft species remains a challenge likely due to the synthetic difficulties toward SPSAs having four-level hierarchical structural transitions and the compromised colloidal stability of the self-assembled quaternary structures. Herein, we report self-assembly of topological polymers with hydrophilic multicycles (HMCs) for biomimetic allostery. Specifically, cationic copolymers containing HMCs are prepared via a reliable synthetic approach, whose hierarchical self-assembly affords stabilized nanoparticles that undergo biomimetic allostery into quaternary petalled self-assemblies at an intracellular acidic pH of 5.0. The quaternary petalled self-assemblies lead to a mechanical disruption effect on lysosomes like nanomachines, further resulting in enhanced drug delivery efficiency of an anticancer drug-loaded multicyclic copolymers with a tumor inhibition rate 1.6-fold greater than that of the free drug in a murine 4T1 model. Overall, our work highlights the use of HMCs as biomimetic allostery of SPSAs for enhanced biomedical applications.