Functionalization of graphene oxide generates a unique interface for selective serum protein interactions.
Potential toxicity and risk of inducing allergy and inflammation have always been a great concern of using nanomaterials in biomedicine. In this work, we investigate the serum behaviors of graphene oxide (GO) and how such behaviors are affected by its surface modification such as PEGylation. The results show that, when incubated with human sera, unfunctionalized GO adsorbs a significant amount of serum proteins and strongly induces complement C3 cleavage (part of the complement activation cascade), generating C3a/C3a(des-Arg), an anaphylatoxin involved in local inflammatory responses, whereas PEGylated nano-GO (nGO-PEG) exhibits dramatic reductions in both protein binding in general and complement C3 activation. Moreover, we uncover that PEGylation on GO nanosheets apparently generates an interesting nanointerface, evidenced by the acquired certain selectivity and increased binding capacities of nGO-PEG toward a few serum proteins. Further mass spectrometry analysis identifies six nGO-PEG binding proteins, four of which are immune-related factors, including C3a/C3a(des-Arg). A series of Western blot analysis demonstrate that nGO-PEG binds up to 2-fold amount of C3a/C3a(des-Arg) than unfunctionalized GO, and can efficiently decrease the level of C3a/C3a(des-Arg) in treated sera, preventing the normal interaction of C3a with its receptor. In a proof-of-concept experiment, we demonstrate that nGO-PEG may serve to help eliminate the C3a/C3a(des-Arg) induced by other nanomaterials such as as-made GO, indicating a new strategy to modulate the immune responses evoked by one nanomaterial through the addition of another type of nanomaterial. Our results highlight the great importance of nanobio interface in regulating the biological effects of nanomaterials.
Institute of Functional Nano & Soft Materials-FUNSOM, Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou, Jiangsu 215123, China.
Xiaofang
X
Tan
Liangzhu
L
Feng
Jing
J
Zhang
Kai
K
Yang
Shuai
S
Zhang
Zhuang
Z
Liu
Rui
R
Peng
D000327:Adsorption; D001798:Blood Proteins / Q000378:metabolism*; D002853:Chromatography, Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D006108:Graphite / Q000737:chemistry*; D010087:Oxides / Q000737:chemistry*; D011485:Protein Binding; D053719:Tandem Mass Spectrometry
D001798:Blood Proteins; D010087:Oxides; D006108:Graphite