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
  • 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. [email protected].
  • 4. Department of Oncology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China. [email protected].
  • 5. National Laboratory of Solid State Microstructures and Department of Physics, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing, Jiangsu, China. [email protected].
  • 6. School of Pharmacy, Department of Pharmaceutics, Nanjing Medical University, Nanjing, Jiangsu, China. [email protected].
  • # 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.

Products