Converting Red Blood Cells to Efficient Microreactors for Blood Detoxification

Abstract

We report a simple method to convert RBCs into efficient microreactors for important biomedical applications. A commonly used cell membrane permeation agent Triton X-100 (TX) was employed at finely tuned concentrations to punch pores in the membranes and render RBCs highly permeable to substrates while maintaining membrane integrity. Subsequently, low concentration of the fixative agent glutaraldehyde (GA) was used to stabilize the cells and avoid inactivation of the membrane proteins. Atomic force microscopy (AFM) and measurement of Young’s modulus (YM) values clearly demonstrated that the reformed RBCs (Ref-RBCs) retained their size, the biconcave disk-like shape, elasticity, and mechanical flexibility comparable to natural RBCs. Furthermore, Ref-RBCs improve the blood survival time of loaded enzymes, and have high permeability to substrate molecules. By exploiting these properties of Ref-RBCs microreactors, we developed an important biomedical application of blood detoxification. When uric acid (UA) and KCN were used as endogenous and exogenous toxin models, respectively, Ref-RBCs, loaded with the corresponding detoxifying enzymes, showed much faster toxin clearance rates than the unmodified RBCs both in vitro and in an in vivo animal model. Our results suggest that these microreactors, after confirming biocompatibility, would have promising therapeutic applications, especially in blood and liver-related diseases.

Recent progress in drug delivery

“…BDDS has advantages of high biocompatibility, low immunogenicity, long systematic circulation and lesion targeting64, 65, 66. It has been widely exploited for biomedical applications, including targeted delivery of therapeutics and diagnosis of diseases, tissue regeneration and wound healing, as well as cell microreactor and blood detoxification67, 68, 69, 70, 71. The development of such biomimetic systems is mainly focused on cell membrane-camouflaged nanoparticles, extracellular vesicles, lipoprotein-coated nanoparticles, virus-like nanoparticles, and others.…”

Cell‐Based Bio‐Hybrid Delivery System for Disease Treatments

“…Some researchers also excavated the potential of RBCs as a versatile scaffold for generating microreactors and immune modulatory agents. [ 27–32 ]…”

Supramolecular Detoxification of Macromolecular Biotoxin through the Complexation by a Large‐Sized Macrocycle

“…[8] Among them, enzymes, which are exquisite biocatalysts that decompose substrates efficiently via specific binding, can serve as excellent antidotes against biotoxins. [9] However, some of their intrinsic shortcomings, such as poor stability, short cycle time, and high immunogenicity, are inevitable. [10] To circumvent these limitations, the synthesis of a bionic receptor that can recognize biotoxin seems necessary.…”