Application of a hemolysis assay for analysis of complement activation by perfluorocarbon nanoparticles

ArticleinNanomedicine: nanotechnology, biology, and medicine 10(3) · November 2013with54 Reads
Impact Factor: 6.16 · DOI: 10.1016/j.nano.2013.10.012 · Source: PubMed
Abstract

Unlabelled: Nanoparticles offer new options for medical diagnosis and therapeutics with their capacity to specifically target cells and tissues with imaging agents and/or drug payloads. The unique physical aspects of nanoparticles present new challenges for this promising technology. Studies indicate that nanoparticles often elicit moderate to severe complement activation. Using human in vitro assays that corroborated the mouse in vivo results we previously presented mechanistic studies that define the pathway and key components involved in modulating complement interactions with several gadolinium-functionalized perfluorocarbon nanoparticles (PFOB). Here we employ a modified in vitro hemolysis-based assay developed in conjunction with the mouse in vivo model to broaden our analysis to include PFOBs of varying size, charge and surface chemistry and examine the variations in nanoparticle-mediated complement activity between individuals. This approach may provide the tools for an in-depth structure-activity relationship study that will guide the eventual development of biocompatible nanoparticles. From the clinical editor: Unique physical aspects of nanoparticles may lead to moderate to severe complement activation in vivo, which represents a challenge to clinical applicability. In order to guide the eventual development of biocompatible nanoparticles, this team of authors report a modified in vitro hemolysis-based assay developed in conjunction with their previously presented mouse model to enable in-depth structure-activity relationship studies.

    • "It is known that NPs are subject to the inspection of the immune system and, the complement system is a rapid-acting host defense mechanism that protects the intravascular space and other biological compartments from foreign attackers [101]. In this context, Pham et al. [102] employed a modified in vitro hemolysis-based assay to examine the variations in NP-mediated complement activity between individuals. The assay was applied to perfluorocarbon NPs of varying size, charge and surface chemistry, and might provide the tools for an in-depth structure–activity relationship study. "
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