Programming of Extra- and Intracellular Protein Coronation through Thiol-Independent Ligand Engineering

作者：Mengdie Xue, Yue‐wen Yin, Liuting Zheng, Xinyue Li, Wei Tang, Xuanyi Jin, X L Zhang, Huiyue Zhao, Yu‐qiang Ma, Hong‐Ming Ding, Da Huo · 发表于：Nano Letters · 年份：2025 · DOI：10.1021/acs.nanolett.5c03113 · 被引用次数：3 · 研究领域：Nanoparticle-Based Drug Delivery、Polymer Surface Interaction Studies、Biotin and Related Studies

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.