Modular Assembly of Red Blood Cell Superstructures from Metal–Organic Framework Nanoparticle‐Based Building Blocks

Abstract

Bio/artificial hybrid nanosystems based on biological matter and synthetic nanoparticles (NPs) remain a holy grail of materials science. Herein, inspired by the well‐defined metal–organic framework (MOF) with diverse chemical diversities, the concept of “armored red blood cells” (armored RBCs) is introduced, which are native RBCs assembled within and protected by a functional exoskeleton of interlinked MOF NPs. Exoskeletons are generated within seconds through MOF NP interlocking based on metal‐phenolic coordination and RBC membrane/NP complexation via hydrogen‐bonding interactions at the cellular interface. Armored RBC formation is shown to be generalizable to many classes of MOF NPs or any NPs that can be coated by MOF. Moreover, it is found that armored RBCs preserve the original properties of RBCs (such as oxygen carrier capability and good ex ovo/in vivo circulation property) and show enhanced resistance against external stressors (like osmotic pressure, detergent, toxic NPs, and freezing conditions). By modifying the physicochemical properties of MOF NPs, armored RBCs provide the capability for blood nitric oxide sensing or multimodal imaging. The synthesis of armored RBCs is straightforward, reliable, and reversible and hence, represent a new class of hybrid biomaterials with a broad range of functionalities.

The Chemistry of Reticular Framework Nanoparticles: MOF, ZIF, and COF Materials

“…Many living organisms fabricate molecular architectures to provide exoskeletal protection and structural support for soft tissue 448. Biomimetic mineralization has been introduced to complex bioentities, such as viruses, bacteria, and mammalian cells 452,453,464…”

“…The above‐mentioned strategy is also applicable to highly fragile cells. Recently, the approach has been employed to red blood cells (RBCs),464 which are responsible for oxygen delivery and drug delivery of natural compounds in vertebrates. RBCs are highly sensitive and instable structures that strongly depend on the environment such as the tonicity and reaction conditions.…”

“…While the interaction of single nanoparticles with the RBCs often results in membrane rupture and hemolysis, the new encapsulation approach overcomes this limitation. The application of all above‐mentioned types of nanoparticles lead to intact, unaltered RBCs,464 that are still biologically active in vivo. Additionally, abiotic properties by the employed nanoparticles can be symbiotically added to the RBCs.…”

“…Indeed, the introduction of an exoskeleton to RBCs stabilizes the cells and enables long‐term storage over days without hemolysis. Even after freezing a cell, recovery up to 40% was observed 453a,464. The introduced encapsulation modulates cell‐cell contact and cell‐adhesion.…”

A Decade of Advances in Single‐Cell Nanocoating for Mammalian Cells

“…e) Reproduced with permission. [ 152 ] Copyright 2020, John Wiley and Sons. f) Reproduced with permission.…”