Department of Medicinal Chemistry, University of Minnesota, 308 Harvard Street SE, Minneapolis, MN 55455 (USA).
Angew Chem Int Ed Engl. 2014 May 12;53(20):5112-6. doi: 10.1002/anie.201310645. Epub 2014 Apr 2.
The ability to engineer and re-program the surfaces of cells would provide an enabling synthetic biological method for the design of cell- and tissue-based therapies. A new cell surface-engineering strategy is described that uses lipid-chemically self-assembled nanorings (lipid-CSANs) that can be used for the stable and reversible modification of any cell surface with a molecular reporter or targeting ligand. In the presence of a non-toxic FDA-approved drug, the nanorings were quickly disassembled and the cell-cell interactions reversed. Similar to T-cells genetically engineered to express chimeric antigen receptors (CARS), when activated peripheral blood mononuclear cells (PBMCs) were functionalized with the anti-EpCAM-lipid-CSANs, they were shown to selectively kill antigen-positive cancer cells. Taken together, these results demonstrate that lipid-CSANs have the potential to be a rapid, stable, and general method for the reversible engineering of cell surfaces and cell-cell interactions.
工程和重新编程细胞表面的能力将为设计基于细胞和组织的治疗方法提供一种可行的合成生物学方法。本文描述了一种新的细胞表面工程策略，该策略使用脂质化学自组装纳米环（lipid-CSANs），可用于稳定且可逆地修饰任何带有分子报告器或靶向配体的细胞表面。在非毒性的 FDA 批准药物存在的情况下，纳米环迅速被分解，细胞间的相互作用被逆转。类似于经过基因工程表达嵌合抗原受体（CARS）的 T 细胞，当用抗 EpCAM-脂质-CSANs 功能化激活的外周血单核细胞（PBMC）时，它们被证明能够选择性地杀死抗原阳性的癌细胞。总之，这些结果表明，脂质-CSANs 有可能成为一种快速、稳定且通用的方法，用于可逆地工程化细胞表面和细胞间相互作用。
