Red Blood Cell Membrane as a Biomimetic Nanocoating for Prolonged Circulation Time and Reduced Accelerated Blood Clearance.
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 Fe(3)O(4) nanoparticles (Fe(3)O(4) @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-α) receptor. Fe(3)O(4) @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 Fe(3)O(4) @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.
Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan, 430072, P. R. China.
Lang
L
Rao
State Key Laboratory Breeding Base of Basic Science of Stomatology, Key Laboratory of Oral Biomedicine of Ministry of Education, Department of Oral Maxillofacial Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, 430079, P. R. China.
Lin-Lin
LL
Bu
Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan, 430072, P. R. China.|CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing, 100190, P. R. China.
Jun-Hua
JH
Xu
Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan, 430072, P. R. China.
Bo
B
Cai
State Key Laboratory Breeding Base of Basic Science of Stomatology, Key Laboratory of Oral Biomedicine of Ministry of Education, Department of Oral Maxillofacial Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, 430079, P. R. China.
Guang-Tao
GT
Yu
Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan, 430072, P. R. China.
Xiaolei
X
Yu
Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan, 430072, P. R. China.
Zhaobo
Z
He
Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan, 430072, P. R. China.
Qinqin
Q
Huang
Department of Mechanical Engineering, Johns Hopkins University, Baltimore, 21218, MA, USA.
Andrew
A
Li
Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan, 430072, P. R. China.
Shi-Shang
SS
Guo
State Key Laboratory Breeding Base of Basic Science of Stomatology, Key Laboratory of Oral Biomedicine of Ministry of Education, Department of Oral Maxillofacial Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, 430079, P. R. China.
Wen-Feng
WF
Zhang
Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan, 430072, P. R. China.|Department of Mechanical Engineering, Johns Hopkins University, Baltimore, 21218, MA, USA.
Wei
W
Liu
State Key Laboratory Breeding Base of Basic Science of Stomatology, Key Laboratory of Oral Biomedicine of Ministry of Education, Department of Oral Maxillofacial Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, 430079, P. R. China.
Zhi-Jun
ZJ
Sun
CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing, 100190, P. R. China.
Hao
H
Wang
Department of Mechanical Engineering, Johns Hopkins University, Baltimore, 21218, MA, USA.
Tza-Huei
TH
Wang
Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan, 430072, P. R. China.
Xing-Zhong
XZ
Zhao
D000818:Animals; D040761:Biomimetic Materials / Q000494:pharmacology*; D001775:Blood Circulation / Q000187:drug effects*; D020099:Coated Materials, Biocompatible / Q000494:pharmacology*; D004910:Erythrocyte Membrane / Q000378:metabolism*; D005290:Ferric Compounds / Q000737:chemistry; D057446:Hydrodynamics; D057131:Immune Evasion; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008422:Materials Testing; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity / Q000648:ultrastructure; D011092:Polyethylene Glycols / Q000737:chemistry; D000067996:RAW 264.7 Cells; D055672:Static Electricity; D013997:Time Factors; D014018:Tissue Distribution / Q000187:drug effects
D020099:Coated Materials, Biocompatible; D005290:Ferric Compounds; C000499:ferric oxide; D011092:Polyethylene Glycols
accelerated blood clearance; biomimetic materials; long circulation times; nanocoatings; red blood cell membranes