title: Influence of polyethyleneglycol modification on phagocytic uptake of polymeric nanoparticles mediated by immunoglobulin G and complement activation.
abstract: The purpose of this study is to investigate the influence of polyethyleneglycol (PEG) modification on in vitro phagocytic uptake of polymeric nanoparticles (NPs) mediated by immunoglobulin G (IgG) and complement activation. A series of PEG-modified poly (D, L-lactide-co-glycolide) nanoparticles (PEG-PLGA-NPs) were incubated in pure serum protein or whole serum, and their capacity for adsorbing albumin and the serum total proteins was measured by a bicinchoninic acid (BCA) protein assay. The adsorption of serum total IgG and complement activation was investigated by enzyme-linked immunosorbent assay (ELISA). To measure in vitro uptake, various fluorescently labeled (Nile red) PEG-PLGA-NPs were opsonized by different pre-treated sera and subsequently incubated with phagocytes. The uptake of NPs by macrophages was then measured by fluorescence spectrometry. Longer chain length and appropriate content PEG reduced the adsorption of serum proteins and complement activation by NPs via both the classical and the alternative pathways. The phagocytosis of PEG-PLGA-NPs by murine peritoneal macrophages (MPMs) involved both serum-independent and serum-dependent phagocytosis. PEG modification was shown only to reduce serum-dependent phagocytosis, mainly by inhibiting IgG adsorption and complement activation on NP surfaces, and the effect of complement activation was greater than that of IgG. The results of this study provided new information that may assist in the design of more efficient nano drug carriers for medical applications.
authors.affiliation: College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
authors.forename: Anshu
authors.initials: A
authors.lastname: Yang
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Zhuoya
authors.initials: Z
authors.lastname: Li
authors.forename: Linyu
authors.initials: L
authors.lastname: Jiang
authors.forename: Huibi
authors.initials: H
authors.lastname: Xu
authors.forename: Xiangliang
authors.initials: X
authors.lastname: Yang
mesh_terms: D000327:Adsorption / Q000187:drug effects; D000818:Animals; D003179:Complement C3b / Q000378:metabolism; D015935:Complement C4b / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D019344:Lactic Acid / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D010446:Peptide Fragments / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology*; D011100:Polyglycolic Acid / Q000737:chemistry / Q000494:pharmacology*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012709:Serum Albumin / Q000378:metabolism*
chemical_list: D007074:Immunoglobulin G; D010446:Peptide Fragments; D012709:Serum Albumin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D003179:Complement C3b; D015935:Complement C4b; C032261:complement C4d