Programming of Extra- and Intracellular Protein Coronation through Thiol-Independent Ligand Engineering
Variation in the distal end of ligands can impact biological functions, but the effects of the proximal end of the ligand (PEL) are less clear. This study presents poly(ethylene glycol) (PEG) ligands that bind to gold beyond the gold-thiol chemistry. Biotin-PEG-modified nanomaterials showed unique protein corona-assisted uptake due to the TMSB4x orientation. All-atom molecular dynamics and super-resolution imaging reveal that TMSB4x facilitates receptor-ligand binding by expanding the pocket. Photoproximity labeling with chemoetching confirms PEL-dependent intracellular effects. For PEL as lipoic acid, gold functionalization allows nanomaterials to inhibit microfilament assembly and destabilize organelle contact sites, providing an anticancer effect without chemotherapy.
Authors
- Yu‐qiang Ma (ORCID: https://orcid.org/0000-0002-5433-3199)
- Mengdie Xue
- Liuting Zheng
- Hong‐Ming Ding (ORCID: https://orcid.org/0000-0002-9224-4779)
- Huiyue Zhao
- Xudong Jin (ORCID: https://orcid.org/0000-0002-2647-9262)
- X L Zhang
- Yue‐wen Yin (ORCID: https://orcid.org/0000-0003-4670-2692)
- Da Huo (ORCID: https://orcid.org/0000-0002-6530-0632)
- Xinyue Li (ORCID: https://orcid.org/0000-0001-7362-0532)
- Wei Tang (ORCID: https://orcid.org/0000-0003-3524-7110)
Institutions
- Soochow University (CN)
- National Cerebral and Cardiovascular Center (JP)
- Collaborative Innovation Center of Advanced Microstructures (CN)
- Jinling Institute of Technology (CN)
- Nanjing Medical University (CN)
- Nanjing University (CN)
Publication Details
- Journal
- Nano Letters
- Published
- 2025-08-25
- DOI
- https://doi.org/10.1021/acs.nanolett.5c03113
- Citations
- 1
- Primary Topic
- Nanoparticle-Based Drug Delivery
- Type
- article
- Field-Weighted Citation Impact
- 0.60
Funders
- National Natural Science Foundation of China
- Jinling Institute of Technology