Protective effect of PEGylation against poly(amidoamine) dendrimer-induced hemolysis of human red blood cells.
Poly(amidoamine) (PAMAM) dendrimers are widely used in medical applications. However, dendrimers bearing positively charged surface groups are prone to destabilize cell membrane and cause cell lysis. The lytic effect of dendrimers on red blood cells (RBCs) namely hemolysis is extremely dangerous when administered in vivo. To diminish the hematologic toxicity, we modified PAMAM dendrimers with poly(ethylene glycol) (PEG) of three molecular weights (2k, 5k, and 20k). The protective effect of PEGylation against PAMAM dendrimer-induced hemolysis was studied. RBCs morphology and surface structure were analyzed by optical microscopy (OM) and atomic force microscopy (AFM). The results indicated that PAMAM and PEG-2k modified dendrimers induced hemolysis at 0.1 and 0.5 mg/mL respectively, whereas PEG-5k and PEG-20k modified dendrimers showed no significant difference in hemolysis compared with control even at 5 mg/mL. OM and AFM investigation indicated PAMAM and PEG-2k modified dendrimers caused RBCs aggregation and lysis. However, no changes were observed in the overall shape of RBCs treated with PEG-5k and PEG-20k modified dendrimers. The surface roughness of RBCs treated with PEGylated dendrimers were far lower than that of RBCs treated with PAMAM dendrimers. This study demonstrated that hemocompatibility of PAMAM dendrimers could be greatly enhanced by PEGylation.
Wang
Wei
W
College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
Xiong
Wei
W
Zhu
Yanhong
Y
Xu
Huibi
H
Yang
Xiangliang
X
D001672:Biocompatible Materials / Q000009:adverse effects* / Q000737:chemistry*; D050091:Dendrimers / Q000009:adverse effects* / Q000737:chemistry*; D004903:Erythrocyte Aggregation / Q000187:drug effects; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000648:ultrastructure; D004912:Erythrocytes / Q000187:drug effects / Q000648:ultrastructure; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D008422:Materials Testing; D018625:Microscopy, Atomic Force; D011092:Polyethylene Glycols; D013499:Surface Properties
D001672:Biocompatible Materials; D050091:Dendrimers; C104700:PAMAM Starburst; D011092:Polyethylene Glycols