Effects of the gene carrier polyethyleneimines on structure and function of blood components.
As a synthetic polycation, polyethylenimine (PEI) is currently one of the most effective non-viral gene carriers. For in vivo applications, PEI will enter systemic circulation and interact with various blood components and then affect their individual bio-functions. Up to now, overall and systematic investigation on the interaction of PEI with multiple blood components at cellular, membrane, and molecular levels is lacking, even though it is critically important for the in vivo safety of PEI. To learn a structure-activity relationship, we investigated the effects of PEI with different molecular weight (MW) and shape (branched or linear) on key blood components and function, specifically, on RBC aggregation and morphological change, platelet activation, conformation change of albumin (as a representative of plasma proteins), and blood coagulation process. Additionally, more proteins from plasma were screened and identified to have associations with PEI by a proteomic analysis. It was found that, the PEIs have severe impact on RBC membrane structure, albumin conformation, and blood coagulation process, but do not significantly activate platelets at low concentrations. Furthermore, 41 plasma proteins were identified to have some interaction with PEI. This indicates that, besides albumin, PEI does interact with a variety of blood plasma proteins, and could have unexplored effects on their structures and bio-functions. The results provide good insight into the molecular design and blood safety of PEI and other polycations for in vivo applications.
Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China.
Dagen
D
Zhong
Yanpeng
Y
Jiao
Yi
Y
Zhang
Wei
W
Zhang
Nan
N
Li
Qinhua
Q
Zuo
Qian
Q
Wang
Wei
W
Xue
Zonghua
Z
Liu
D000327:Adsorption / Q000187:drug effects; D000818:Animals; D001769:Blood / Q000187:drug effects*; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D002417:Cattle; D048430:Cell Shape / Q000187:drug effects; D002942:Circular Dichroism; D004591:Electrophoresis, Polyacrylamide Gel; D004903:Erythrocyte Aggregation / Q000187:drug effects*; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D018014:Gene Transfer Techniques; D006801:Humans; D007700:Kinetics; D015539:Platelet Activation / Q000187:drug effects*; D011094:Polyethyleneimine / Q000494:pharmacology*; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet
D012710:Serum Albumin, Bovine; D011094:Polyethyleneimine