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  3. Nanomaterial signatures program biomolecular condensates via triphasic separation for chemoplasticity remodeling

Nanomaterial signatures program biomolecular condensates via triphasic separation for chemoplasticity remodeling

  • Nat Commun. 2025 Oct 29;16(1):9554. doi: 10.1038/s41467-025-64623-4.
Liu-Ting Zheng # 1,  Zeng-Shuai Yan # 2,  Xin-Yue Li # 1,  Jia-Jia Chang 1,  Xiao-Qi Tan 1,  Yu-Xing Wang 1,  Hong-Ming Ding 3,  Qin Liu 4,  Yu-Qiang Ma 5,  Da Huo 6
Affiliations

Affiliations

  • 1 School of Pharmacy, Department of Pharmaceutics, Nanjing Medical University, Nanjing, Jiangsu, China.
  • 2 Center for Soft Condensed Matter Physics and Interdisciplinary Research, School of Physical Science and Technology, Soochow University, Suzhou, Jiangsu, China.
  • 3 Center for Soft Condensed Matter Physics and Interdisciplinary Research, School of Physical Science and Technology, Soochow University, Suzhou, Jiangsu, China. dinghm@suda.edu.cn.
  • 4 Department of Oncology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China. liuqin@nju.edu.cn.
  • 5 National Laboratory of Solid State Microstructures and Department of Physics, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing, Jiangsu, China. myqiang@nju.edu.cn.
  • 6 School of Pharmacy, Department of Pharmaceutics, Nanjing Medical University, Nanjing, Jiangsu, China. huoda@njmu.edu.cn.
  • # Contributed equally.
PMID: 41162367 DOI: 10.1038/s41467-025-64623-4
Abstract

Membraneless organelles form by phase separation and regulate cell behavior. We show that cholesterol-patterned AuNPs program nanomaterial-induced stress granules (NSGs) by lowering G3BP1 condensation barriers through a solid-liquid-liquid triphasic sequence: nanomaterials recruit hnRNPC, which then engages G3BP1 to nucleate gel-like condensates. We map NSG microenvironments (temperature, polarity, pH, and Proteasome activity), uncover dual disassembly-a slow VCP/19S-dependent route and a rapid SUMO/20S-dependent backup-and show that NSGs remodel chemo-plasticity: they mitigate doxorubicin/cisplatin toxicity in normal tissues yet sensitize tumors to nocodazole in vivo. Local induction and selective dissolution of NSGs thus offers a strategy to decouple efficacy from toxicity. Our results establish design rules linking nanomaterial surface chemistry to condensate programming and provide actionable levers to steer therapeutic outcomes.

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