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Biomaterials. 2011 Mar;32(8):2194-203. doi: 10.1016/j.biomaterials.2010.11.037. Epub 2010 Dec 22.

Engineering complement activation on polypropylene sulfide vaccine nanoparticles.

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1
Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Station 15, Lausanne CH 1015, Switzerland.

Abstract

The complement system is an important regulator of both adaptive and innate immunity, implicating complement as a potential target for immunotherapeutics. We have recently presented lymph node-targeting, complement-activating nanoparticles (NPs) as a vaccine platform. Here we explore modulation of surface chemistry as a means to control complement deposition, in active or inactive forms, on polypropylene sulfide core, block copolymer Pluronic corona NPs. We found that nucleophile-containing NP surfaces activated complement and became functionalized in situ with C3 upon serum exposure via the alternative pathway. Carboxylated NPs displayed a higher degree of C3b deposition and retention relative to hydroxylated NPs, upon which deposited C3b was more substantially inactivated to iC3b. This in situ functionalization correlated with in vivo antigen-specific immune responses, including antibody production as well as T cell proliferation and IFN-γ cytokine production upon antigen restimulation. Interestingly, inactivation of C3b to iC3b on the NP surface did not correlate with NP affinity to factor H, a cofactor for protease factor I that degrades C3b into iC3b, indicating that control of complement protein C3 stability depends on architectural details in addition to factor H affinity. These data show that design of NP surface chemistry can be used to control biomaterials-associated complement activation for immunotherapeutic materials.

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