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

Abstract 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 t...

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Bibliographic Details
Published in:Nanomedicine 2014-04, Vol.10 (3), p.651-660
Main Authors: Pham, Christine T.N., MD, Thomas, Dennis G., PhD, Beiser, Julia, MS, Mitchell, Lynne M., MS, Huang, Jennifer L., BS, Senpan, Angana, PhD, Hu, Grace, MS, Gordon, Mae, PhD, Baker, Nathan A., PhD, Pan, Dipanjan, PhD, Lanza, Gregory M., MD, PhD, Hourcade, Dennis E., PhD
Format: Article
Language:English
Subjects:
Animals
Complement
Complement Activation - drug effects
Fluorocarbons - chemistry
Fluorocarbons - immunology
Hemolysis - drug effects
Hemolysis Assay
Humans
Internal Medicine
Mice
Mice, Inbred C57BL
Mouse Model
Nanomedicine
Nanoparticles
Nanoparticles - chemistry
Nanoparticles - metabolism
Particle Size
Perfluorocarbon
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Summary:Abstract 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.
ISSN:1549-9634
1549-9642
DOI:10.1016/j.nano.2013.10.012