Distinct polymer architecture mediates switching of complement activation pathways at the nanosphere-serum interface: Implications for stealth nanoparticle engineering

Islam Hamad, Othman Al-Hanbali, A. Christy Hunter, Kenneth J. Rutt, Thomas L. Andresen, S. Moein Moghimi

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Nanoparticles with surface projected polyethyleneoxide (PEO) chains in "mushroom-brush" and "brush" configurations display stealth properties in systemic circulation and have numerous applications in site-specific targeting for controlled drug delivery and release as well as diagnostic imaging. We report on the "structure-activity" relationship pertaining to surface-immobilized PEO of various configurations on model nanoparticles, and the initiation of complement cascade, which is the most ancient component of innate human immunity, and its activation may induce clinically significant adverse reactions in some individuals. Conformational states of surface-projected PEO chains, arising from the block copolymer poloxamine 908 adsorption, on polystyrene nanoparticles trigger complement activation differently. Alteration of copolymer architecture on nanospheres from mushroom to brush configuration not only switches complement activation from C1q-dependent classical to lectin pathway but also reduces the level of generated complement activation products C4d, Bb, C5a, and SC5b-9. Also, changes in adsorbed polymer configuration trigger alternative pathway activation differently and through different initiators. Notably, the role for properdin-mediated activation of alternative pathway was only restricted to particles displaying PEO chains in a transition mushroom-brush configuration. Since nanoparticle-mediated complement activation is of clinical concern, our findings provide a rational basis for improved surface engineering and design of immunologically safer stealth and targetable nanosystems with polymers for use in clinical medicine. © 2010 American Chemical Society.
    Original languageEnglish
    Pages (from-to)6629-6638
    Number of pages9
    JournalACS Nano
    Volume4
    Issue number11
    DOIs
    Publication statusPublished - 23 Nov 2010

    Keywords

    • Block copolymers
    • Complement activation
    • Nanomedicine
    • Poloxamine 908
    • Stealth nanoparticles

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