John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138, USA.
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA.
Adv Mater. 2020 Dec;32(49):e2003492. doi: 10.1002/adma.202003492. Epub 2020 Nov 4.
Approaches to safely and effectively augment cellular functions without compromising the inherent biological properties of the cells, especially through the integration of biologically labile domains, remain of great interest. Here, a versatile strategy to assemble biologically active nanocomplexes, including proteins, DNA, mRNA, and even viral carriers, on cellular surfaces to generate a cell-based hybrid system referred to as "Cellnex" is established. This strategy can be used to engineer a wide range of cell types used in adoptive cell transfers, including erythrocytes, macrophages, NK cells, T cells, etc. Erythrocyte can enhance the delivery of cargo proteins to the lungs in vivo by 11-fold as compared to the free cargo counterpart. Biomimetic microfluidic experiments and modeling provided detailed insights into the targeting mechanism. In addition, Macrophage is capable of enhancing the therapeutic efficiency of anti-PD-L1 checkpoint inhibitors in vivo. This simple and adaptable approach may offer a platform for the rapid generation of complex cellular systems.
安全有效地增强细胞功能而不损害细胞固有生物学特性的方法仍然非常重要，特别是通过整合生物不稳定结构域。在这里，建立了一种将包括蛋白质、DNA、mRNA 甚至病毒载体在内的生物活性纳米复合物组装到细胞表面上以生成称为“Cellnex”的基于细胞的杂交系统的通用策略。该策略可用于工程化各种用于过继细胞转移的细胞类型，包括红细胞、巨噬细胞、NK 细胞、T 细胞等。与游离货物相比，红细胞可使货物蛋白在体内向肺部的递呈增加 11 倍。仿生微流控实验和建模提供了对靶向机制的详细见解。此外，巨噬细胞能够增强抗 PD-L1 检查点抑制剂在体内的治疗效果。这种简单且适应性强的方法可能为快速生成复杂细胞系统提供平台。
