Engineering complement activation on polypropylene sulfide vaccine nanoparticles

Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Station 15, Lausanne CH 1015, Switzerland.
Biomaterials (Impact Factor: 8.56). 03/2011; 32(8):2194-203. DOI: 10.1016/j.biomaterials.2010.11.037
Source: OAI


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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Available from: Shann S Yu, Mar 06, 2014
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    • "Pluronic-stabilized poly(propylene sulfide) (PPS) NPs with average diameters of 30 nm were synthesized by inverse emulsion polymerization as described previously [21,22,32,39,40]. Pluronic F-127 (a block copolymer of polyethylene glycol and polypropylene glycol terminated by hydroxyl groups) was used alone or in combination with carboxyl-terminated Pluronic derivatized as previously described [22] [39] [40]. Polymerization in the hydrophobic core results in PPS chains with a terminal thiolate, which can lead to stabilization of the core by intermolecular disulfide crosslinking [39]. "
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