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Overcoming Nanoparticle-Mediated Complement Activation by Surface PEG Pairing
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DOI：10.1021/acs.nanolett.0c01011.png)
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Abstract
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Many PEGylated nanoparticles activate the complement system, which is an integral component of innate immunity. This is of concern as uncontrolled complement activation is potentially detrimental and contributes to disease pathogenesis. Here, it is demonstrated that, in contrast to carboxyPEG(2000) stabilized poly(lactic-co-glycolic acid) nanoparticles, surface camouflaging with appropriate combinations and proportions of carboxyPEG(2000) and methoxyPEG(550) can largely suppress nanoparticle-mediated complement activation through the lectin pathway. This is attributed to the ability of the short, rigid methoxyPEG(550) chains to laterally compress carboxyPEG(2000) molecules to become more stretched and assume an extended, A random coil configuration. As supported by coarse-grained molecular dynamics simulations, these conformational attributes minimize statistical protein binding/intercalation, thereby affecting sequential dynamic processes in complement convertase assembly. Furthermore, PEG pairing has no additional effect on nanoparticle longevity in the blood and macrophage uptake. PEG pairing significantly overcomes nanoparticle-mediated complement activation without the need for surface functionalization with complement inhibitors.
Keywords:
nanoparticles
surface engineering
PEG conformation
protein absorption
complement lectin pathway
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Complement proteins bind to nanoparticle protein corona and undergo dynamic exchange in vivo.png)
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