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Influence of Polyethyleneglycol Modification on Phagocytic Uptake of Polymeric Nanoparticles Mediated by Immunoglobulin G and Complement Activation

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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.

Keywords: COMPLEMENT ACTIVATION; IGG; NANOPARTICLES; PHAGOCYTIC UPTAKE; POLYETHYLENEGLYCOL MODIFICATION

Document Type: Research Article

DOI: http://dx.doi.org/10.1166/jnn.2010.1738

Publication date: January 1, 2010

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  • Journal for Nanoscience and Nanotechnology (JNN) is an international and multidisciplinary peer-reviewed journal with a wide-ranging coverage, consolidating research activities in all areas of nanoscience and nanotechnology into a single and unique reference source. JNN is the first cross-disciplinary journal to publish original full research articles, rapid communications of important new scientific and technological findings, timely state-of-the-art reviews with author's photo and short biography, and current research news encompassing the fundamental and applied research in all disciplines of science, engineering and medicine.
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