Overcoming Nanoparticle-mediated complement activation by surface PEG pairing

Martina Pannuzzo, Sara Esposito, Lin Ping Wu, Jaehong Key, Santosh Aryal, Christian Celia, Luisa Di Marzio, Seyed Moein Moghimi, Paolo Decuzzi

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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 carboxyPEG2000- stabilized poly(lactic-co-glycolic acid) nanoparticles, surface camouflaging with appropriate combinations and proportions of carboxyPEG2000 and methoxyPEG550 can largely suppress nanoparticle- mediated complement activation through the lectin pathway. This is attributed to the ability of the short, rigid methoxyPEG550 chains to laterally compress carboxyPEG2000 molecules to become more stretched and assume an extended, 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.

Original languageEnglish
Pages (from-to)4312-4321
Number of pages10
JournalNano letters
Volume20
Issue number6
DOIs
Publication statusPublished - 2020

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics
  • Mechanical Engineering

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  • Cite this

    Pannuzzo, M., Esposito, S., Wu, L. P., Key, J., Aryal, S., Celia, C., Di Marzio, L., Moghimi, S. M., & Decuzzi, P. (2020). Overcoming Nanoparticle-mediated complement activation by surface PEG pairing. Nano letters, 20(6), 4312-4321. https://doi.org/10.1021/acs.nanolett.0c01011