Guo Jimin, Agola Jacob Ongudi, Serda Rita, Franco Stefan, Lei Qi, Wang Lu, Minster Joshua, Croissant Jonas G, Butler Kimberly S, Zhu Wei, Brinker C Jeffrey
Center for Micro-Engineered Materials, Department of Chemical and Biological Engineering, University of New Mexico, Albuquerque, New Mexico 87131, United States.
Department of Internal Medicine, Molecular Medicine, University of New Mexico, Albuquerque, New Mexico 87131, United States.
ACS Nano. 2020 Jul 28;14(7):7847-7859. doi: 10.1021/acsnano.9b08714. Epub 2020 May 11.
The design and synthesis of artificial materials that mimic the structures, mechanical properties, and ultimately functionalities of biological cells remains a current holy grail of materials science. Here, based on a silica cell bioreplication approach, we report the design and construction of synthetic rebuilt red blood cells (RRBCs) that fully mimic the broad properties of native RBCs: size, biconcave shape, deformability, oxygen-carrying capacity, and long circulation time. Four successive nanoscale processing steps (RBC bioreplication, layer-by-layer polymer deposition, and precision silica etching, followed by RBC ghost membrane vesicle fusion) are employed for RRBC construction. A panel of physicochemical analyses including zeta-potential measurement, fluorescence microscopy, and antibody-mediated agglutination assay proved the recapitulation of RBC shape, size, and membrane structure. Flow-based deformation studies carried out in a microfluidic blood capillary model confirmed the ability of RRBCs to deform and pass through small slits and reconstitute themselves in a manner comparable to native RBCs. Circulation studies of RRBCs conducted in a chick embryo and in a mouse model demonstrated the requirement of both deformability and native cell membrane surface to achieve long-term circulation. To confer additional non-native functionalities to RRBCs, we developed modular procedures with which to load functional cargos such as hemoglobin, drugs, magnetic nanoparticles, and ATP biosensors within the RRBC interior to enable various functions, including oxygen delivery, therapeutic drug delivery, magnetic manipulation, and toxin biosensing and detection. Taken together, RRBCs represent a class of long-circulating RBC-inspired artificial hybrid materials with a broad range of potential applications.
设计和合成能够模仿生物细胞结构、力学性能并最终实现其功能的人工材料，仍然是材料科学当前的圣杯。在此，基于二氧化硅细胞生物复制方法，我们报告了合成重建红细胞（RRBCs）的设计与构建，其全面模仿了天然红细胞的广泛特性：大小、双凹形状、可变形性、携氧能力和长循环时间。RRBCs的构建采用了四个连续的纳米级处理步骤（红细胞生物复制、逐层聚合物沉积、精密二氧化硅蚀刻，随后进行红细胞空壳膜囊泡融合）。包括zeta电位测量、荧光显微镜检查和抗体介导的凝集试验在内的一系列物理化学分析证明了红细胞形状、大小和膜结构的重现。在微流控毛细血管模型中进行的基于流动的变形研究证实，RRBCs能够变形并穿过小缝隙，并以与天然红细胞相当的方式自我重构。在鸡胚和小鼠模型中进行的RRBCs循环研究表明，要实现长期循环，既需要可变形性，也需要天然细胞膜表面。为了赋予RRBCs额外的非天然功能，我们开发了模块化程序，用于在RRBC内部装载血红蛋白、药物、磁性纳米颗粒和ATP生物传感器等功能性货物，以实现各种功能，包括氧气输送、治疗药物递送、磁操纵以及毒素生物传感和检测。综上所述，RRBCs代表了一类受红细胞启发的长循环人工杂化材料，具有广泛的潜在应用。
