Complement therapeutics meets nanomedicine: overcoming human complement activation and leukocyte uptake of nanomedicines with soluble domains of CD55.

ABSTRACT: Complement activation plays an important role in pharmacokinetic and performance of intravenously administered nanomedicines. Significant efforts have been directed toward engineering of nanosurfaces with low complement activation, but due to promiscuity of complement factors and redundancy of pathways, it is still a major challenge. Cell membrane-anchored Decay Accelerating Factor (DAF, a.k.a. CD55) is an efficient membrane bound complement regulator that inhibits both classical and alternative C3 convertases by accelerating their spontaneous decay. Here we tested the effect of various short consensus repeats (SCRs, "sushi" domains) of human CD55 on nanoparticle-mediated complement activation in human sera and plasma. Structural modeling suggested that SCR-2, SCR-3 and SCR-4 are critical

SUBMITTER: Gifford G 

PROVIDER: S-EPMC6684249 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature