Frontiers Science Center for Synthetic Biology, Key Laboratory of Systems Bioengineering (MOE), Institute of Biomolecular and Biomedical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300350, People's Republic of China.
J Am Chem Soc. 2021 Nov 24;143(46):19330-19340. doi: 10.1021/jacs.1c07036. Epub 2021 Nov 15.
The efficient isolation of immune cells with high purity and low cell damage is important for immunotherapy and remains highly challenging. We herein report a cell capture DNA network containing polyvalent multimodules for the specific isolation and incubation of T lymphocytes (T-cells). Two ultralong DNA chains synthesized by an enzymatic amplification process were rationally designed to include functional multimodules as cell anchors and immune adjuvants. Mutually complementary sequences facilitated the formation of a DNA network and encapsulation of T-cells, as well as offering cutting sites of a restriction enzyme for the responsive release of T-cells and immune adjuvants. The purity of captured tumor-infiltrating T-cells reached 98%, and the viability of T-cells maintained ∼90%. The T-cells-containing DNA network was further administrated to a tumor lesion for localized immunotherapy. Our work provides a robust nanobiotechnology for efficient isolation of immune cells and other biological particles.
高效分离高纯度、低细胞损伤的免疫细胞对于免疫治疗非常重要,但这仍然极具挑战性。本文报道了一种包含多价多模块的细胞捕获 DNA 网络,用于 T 淋巴细胞(T 细胞)的特异性分离和孵育。通过酶促扩增过程合成的两条超长 DNA 链被合理设计,包含作为细胞锚定物和免疫佐剂的功能多模块。互补序列促进了 DNA 网络的形成和 T 细胞的封装,同时提供了限制酶的切割位点,以响应性地释放 T 细胞和免疫佐剂。捕获的肿瘤浸润 T 细胞的纯度达到 98%,T 细胞的活力保持在约 90%。含有 T 细胞的 DNA 网络进一步用于肿瘤病变的局部免疫治疗。我们的工作为高效分离免疫细胞和其他生物颗粒提供了一种强大的纳米生物技术。