Influence of PEG chain on the complement activation suppression and longevity in vivo prolongation of the PCL biomedical nanoparticles.
The process of opsonization is the major biological barrier to the injectable polymeric nanoparticles (NPs). Complement protein is one kind of opsonins and it can be activated potentially by the negative charged particles. The fragment C3b generated by complement activation could subsequently induce the opsonization on the NPs surface. The aim of our work was to examine the relationship between the hydrophilic poly(ethylene glycol) (PEG) chain on the surface of NPs and particles longevity in vivo from the biological point of view such as complement activation (C3 cleavage) as well as uptake by macrophages. The studies showed that the introduction of PEG chains led to slightly smaller NPs with lower polydispersities than those prepared from naked poly(epsilon-caprolactone) (PCL) and enhanced the zeta potential of NPs from -27.17 mV to -6.046 mV. It was also found that PEG hydrophilic chain could decrease the C3 cleavage and remarkably suppress opsonization and phagocytosis subsequently. In biodistribution investigations in vivo, as a control, PCL NPs were present in MPS tissues in the first 5 min followed by metabolism elimination rapidly, whereas the PEGylated NPs had more particles blood retention in vivo after injection. In fact, in present work, it has been convinced that these results in vivo could be predicted by the in vitro fluorescent phagocytosis model and the extent of complement activation in advance.
Shan
Xiaoqian
X
The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, People's Republic of China.
Yuan
Yuan
Y
Liu
Changsheng
C
Tao
Xinyi
X
Sheng
Yan
Y
Xu
Feng
F
D000818:Animals; D003167:Complement Activation; D003176:Complement C3 / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D012157:Mononuclear Phagocyte System / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D010587:Phagocytosis; D011091:Polyesters / Q000737:chemistry* / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000737:chemistry*; D014018:Tissue Distribution
D003176:Complement C3; D011091:Polyesters; C016240:polycaprolactone; D011092:Polyethylene Glycols