期刊
SMALL
卷 11, 期 46, 页码 6225-6236出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/smll.201502388
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资金
- National Natural Science Foundation of China [51272184, 81272443, 81272963, 81272964]
- State Key Program of National Natural Science of China [51132001]
- National Science Fund for Talent Training in Basic Science [J1210061]
For decades, poly(ethylene glycol) (PEG) has been widely incorporated into nanoparticles for evading immune clearance and improving the systematic circulation time. However, recent studies have reported a phenomenon known as accelerated blood clearance (ABC) where a second dose of PEGylated nanomaterials is rapidly cleared when given several days after the first dose. Herein, we demonstrate that natural red blood cell (RBC) membrane is a superior alternative to PEG. Biomimetic RBC membrane-coated Fe3O4 nanoparticles (Fe3O4 @ RBC NPs) rely on CD47, which is a don't eat me marker on the RBC surface, to escape immune clearance through interactions with the signal regulatory protein-alpha (SIRP-alpha) receptor. Fe3O4 @ RBC NPs exhibit extended circulation time and show little change between the first and second doses, with no ABC suffered. In addition, the administration of Fe3O4 @ RBC NPs does not elicit immune responses on neither the cellular level (myeloid-derived suppressor cells (MDSCs)) nor the humoral level (immunoglobulin M and G (IgM and IgG)). Finally, the in vivo toxicity of these cell membrane-camouflaged nanoparticles is systematically investigated by blood biochemistry, hematology testing, and histology analysis. These findings are significant advancements toward solving the long-existing clinical challenges of developing biomaterials that are able to resist both immune response and rapid clearance.
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