期刊
JOURNAL OF CONTROLLED RELEASE
卷 287, 期 -, 页码 121-131出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2018.08.022
关键词
Anti-drug antibodies (ADA); Poly(ethylene glycol)-b-poly(lactic co glycolic acid) (PEG-PLGA); Nanoparticles; Drug delivery; Pharmacokinetics; Biodistribution; Liposomes
资金
- Natural Sciences and Engineering Research Council (NSERC) of Canada
- Canadian Funds for Innovation (CFI)
- Fondation du CHU de Quebec
- Fondation du CHU de Quebec-Desjardins
- Fonds d'Enseignement et de Recherche of the Faculty of Pharmacy of Laval University, Canada
- Doctoral Program Abroad / CAPES Foundation within Ministry of Education of Brazil [88881.132236/2016-01]
Multiple studies highlight the strong prevalence of anti-poly(ethylene glycol) (anti-PEG) antibodies in the general human population. As we develop therapeutic modalities using this polymer, it is increasingly relevant to assess the importance of anti-PEG antibodies on biological performances. Here, we show that the anti-PEG Immunoglobulin M (IgM) raised in mice following the injection of polymeric nanoparticles could have significant neutralizing effects on subsequent doses of PEGylated nanosystems in vivo. The circulation times of PEGylated nanoparticles and liposomes were strongly reduced in animals with circulating anti-PEG IgMs, irrespective of the PEG density or the surface properties of the system. In comparison, despite that anti-PEG IgMs could bind free methoxy-terminated PEG and PEGylated bovine serum albumin, the circulation kinetics of these systems remained unaltered in the presence of antibodies. The binding of IgMs to the PEGylated surface of nanoparticles alters the nature of the proteins adsorbed in the surrounding corona, notably due to the activation of the complement cascade. These changes are responsible for the observed differences in circulation times. In comparison, the PEG-BSA is unable to activate complement, even in the presence of anti-PEG IgMs. These results inform on how anti-PEG antibodies can affect the fate of PEGylated nanomaterials and highlight how the architecture of nanoparticles impacts the deposition of the protein corona.
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