Modular assembly of red blood cells with metal-organic frameworks

A closer look inside living matter has revealed that basic units of living beings, such as proteins, nucleic acids, and macromolecular assemblies, have sizes on the nanometer scale. Interestingly, these basic units present spectacular reactivity and chemical specificity that were naturally optimized through life evolution. However natural evolution has so far failed to incorporate into living systems the extraordinary diversity of synthetic nanomaterials. By expanding the palette of building blocks of living systems we expect to create new non-native living phenotypes with as yet unknown but potentially limitless properties.

In this article:

Advanced Functional Materials 2021, 31 (10), 2005935

we report a simple, generalizable approach to modify natural red blood cells (RBCs) with synthetic metal-organic framework nanoparticles (MOF NPs) along with other silica and iron NPs. The synergistic combination of natural RBCs and MOFs exploits the advantageous properties of each system to create a tunable living platform for different biological applications. The resulting “Armored RBCs” display the natural in vitro and in vivo properties of RBC (e.g. oxygen carrying capacity and long circulation times) but at the same time the beneficial properties of MOF NPs, namely their organic-inorganic hybrid nature, structural diversity, high surface area, tunable porosity, biodegradability and importantly cargo carrying capacity based on modification of the inner and outer MOF surfaces. We demonstrate that Armored RBCs show significant enhanced resistance against exogenous stresses such as: antibody-mediated agglutination, osmotic pressure, detergents, toxic NPs, and freezing conditions. Further, we can endow them with diagnostic properties such as blood nitric oxide (NO) sensing and, through modification with magnetic or fluorescently labeled NPs, we can create new classes of contrast agents and imaging agents for magnetic resonance imaging and live-cell imaging, respectively. In addition, the synthesis of Armored RBCs is completely reversible allowing the Armored RBCs to disassemble in vivo serving as a long circulating source of potentially therapeutic NPs.

Overall, the article contributes to our understanding of how to integrate artificial nanometer sized building blocks with cells to create a new class of living biomolecular systems. We estimate that our approach can constitute a significant turning point in the synthesis of flexible multifunctional nanoparticle platforms for different biological applications.

Figure. a) Schematic representation of the assembly of red blood cells with metal-organic framework nanoparticles into Armored RBC. Schematic illustration of the properties of Armored RBCs: in vivo circulation (b), oxygen delivery (c), particle hitchhiking and redistribution (d), and enhanced resistance against external stressors and blood NO sensing (e).