Biomimetic Rebuilding of Multifunctional Red Blood Cells: Modular Design Using Functional Components
Biomimetic Rebuilding of Multifunctional Red Blood Cells: Modular Design Using Functional Components
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多功能红细胞的仿生重建：使用功能组件的模块化设计
DOI：
10.1021/acsnano.9b08714
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发表时间：
2020-07-28
期刊：
影响因子：
17.1
通讯作者：
Brinker, C. Jeffrey
中科院分区：
文献类型：
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作者：
Guo, Jimin;Agola, Jacob Ongudi;Brinker, C. Jeffrey
人工材料的设计和合成模仿生物细胞的结构、机械性能和最终功能，仍然是当前材料科学的圣杯。在这里，基于硅胶细胞生物复制方法，我们报道了人工重建红细胞(RRBCs)的设计和构建，它完全模拟了天然红细胞的广泛特性：大小、双凹形状、变形性、携氧能力和长循环时间。RBC的构建采用了四个连续的纳米级处理步骤(RBC生物复制、层层聚合物沉积和精密二氧化硅刻蚀，然后是RBC鬼膜囊泡融合)。包括Zeta电位测量、荧光显微镜和抗体介导的凝集试验在内的一组物理化学分析证实了红细胞的形状、大小和膜结构的重现。在微流体毛细血管模型中进行的基于流动的变形研究证实了红细胞变形和通过小缝隙并以与天然红细胞相当的方式重建自身的能力。在鸡胚胎体外和小鼠模型体内进行的RRBCs的循环研究表明，实现长期循环既需要变形能力，也需要天然细胞膜表面。为了赋予RRBCs额外的非本地功能，我们开发了模块化程序，用于在RRBC内部装载功能货物，如血红蛋白、药物、磁性纳米颗粒和ATP生物传感器，以实现各种功能，包括氧气输送、治疗性药物输送、磁性操纵以及毒素生物传感和检测。综上所述，RRBCs代表了一类长期循环的以RBC为灵感的人工杂化材料，具有广泛的潜在应用。
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 ex ovo in a chick embryo and in vivo 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.