Bioconjug Chem. 2018 Apr 18;29(4):1291-1301. doi: 10.1021/acs.bioconjchem.8b00058. Epub 2018 Mar 23.
Membrane-engineered cells displaying antigen-targeting ligands are useful as both scientific tools and clinical therapeutics. While genetically encoded artificial receptors have proven efficacious, their scope remains limited, as this approach is not amenable to all cell types and the modification is often permanent. Our group has developed a nongenetic method to rapidly, stably, and reversibly modify any cell membrane with a chemically self-assembled nanoring (CSAN) that can function as a prosthetic receptor. Bifunctional CSANs displaying epithelial cell adhesion molecule (EpCAM)-targeted fibronectin domains were installed on the cell membrane through hydrophobic insertion and remained stably bound for ≥72 h in vitro. These CSAN-labeled cells were capable of recognizing EpCAM-expressing target cells, forming intercellular interactions that were subsequently reversed by disassembling the nanoring with the FDA-approved antibiotic, trimethoprim. This study demonstrates the use of this system to engineer cell surfaces with prosthetic receptors capable of directing specific and reversible cell-cell interactions.
展示抗原靶向配体的膜工程细胞可用作科学工具和临床治疗剂。虽然遗传编码的人工受体已被证明有效，但它们的应用范围仍然有限，因为这种方法不适用于所有细胞类型，而且修饰通常是永久性的。我们的小组开发了一种非遗传方法，可以快速、稳定且可逆地用可化学自组装纳米环（CSAN）修饰任何细胞膜，该纳米环可用作假体受体。通过疏水性插入将展示上皮细胞黏附分子（EpCAM）靶向性纤维连接蛋白结构域的双功能 CSAN 安装在细胞膜上，在体外至少稳定结合 72 小时。这些 CSAN 标记的细胞能够识别表达 EpCAM 的靶细胞，形成细胞间相互作用，随后用已批准用于临床的抗生素甲氧苄啶（trimethoprim）将纳米环拆开，从而逆转这种相互作用。这项研究展示了使用该系统在细胞表面工程化具有假体受体的能力，这些受体能够指导特定和可逆的细胞-细胞相互作用。
