TY - JOUR
T1 - Biomimetic Rebuilding of Multifunctional Red Blood Cells
T2 - Modular Design Using Functional Components
AU - Guo, Jimin
AU - Agola, Jacob Ongudi
AU - Serda, Rita
AU - Franco, Stefan
AU - Lei, Qi
AU - Wang, Lu
AU - Minster, Joshua
AU - Croissant, Jonas G.
AU - Butler, Kimberly S.
AU - Zhu, Wei
AU - Brinker, C. Jeffrey
N1 - Funding Information:
We thank Prof. Jiwei Cui in Shandong University for providing the microfluidic blood capillary model. We acknowledge the financial support from the Air Force Office of Scientific Research under Grant No. FA9550-14-1-0066 and the Laboratory Directed Research Development Program at Sandia National Laboratories. We also acknowledge support from the Department of Energy Office of Science, Division of Materials Science and Engineering. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the U.S. Department of Energy or the United States Government. Sandia National Laboratories (SNL) is a multimission laboratory managed and operated by National Technology and Engineering Solutions of Sandia, LLC, a wholly owned subsidiary of Honey-well International, Inc., for the U.S. Department of Energy’s National Nuclear Security Administration under contract DENA-0003525. W.Z. acknowledges the financial support from National Natural Science Foundation of China (21972047).
Publisher Copyright:
Copyright © 2020 American Chemical Society.
PY - 2020/7/28
Y1 - 2020/7/28
N2 - 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.
AB - 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.
KW - bioapplications
KW - biomimicry
KW - drug carrier
KW - multifunction
KW - red blood cells
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U2 - 10.1021/acsnano.9b08714
DO - 10.1021/acsnano.9b08714
M3 - Article
C2 - 32391687
AN - SCOPUS:85085597410
VL - 14
SP - 7847
EP - 7859
JO - ACS Nano
JF - ACS Nano
SN - 1936-0851
IS - 7
ER -