Development of a Sensitive Assay to Screen Nanoparticles in vitro for Complement Activation
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Single Donor Human Whole Blood, Single Donor Human Plasma (Blood Derived), Single Donor Human Complement Serum, Innovative Grade US Origin Porcine Plasma, and Innovative Grade US Origin Porcine Whole Blood from Innovative Research were used in the following study:
Development of a Sensitive Assay to Screen Nanoparticles in vitro for Complement Activation
Nuzhat Maisha, Tobias Coombs, and Erin B. Lavik
American Chemical Society
July 6, 2020
Nanomedicines are often recognized by the innate immune system as a threat, leading to unwanted clearance due to complement activation. This unwanted reaction not only alters the bioavailability of the therapeutic, but can also cause cardiopulmonary complications and death in a portion of the population. The cardiopulmonary distress results from changes in arterial blood gas, vitals and increases in blood vessel permeability, which lead to vasodilation. This reaction is due, at least in part, to initial intravenous infusion of nanomaterials triggering the complement pathway, a part of the innate immune system.
There is a need for tools for assessing complement response in the early stage of development of nanomedicines. Currently, quantifying complement-mediated response in vitro is limited due to differences between in vitro and in vivo responses for the same precursors, differences in the complement systems in different species, and lack of highly sensitive tools for quantifying the changes.
The three most common methods for measuring complement activation are indirect measurement through hemolysis assay, quantifying the proteins that attach to the nanoparticle surface, and through enzyme immunoassays. These methods use nanoparticle blood interaction to generate complement proteins, and then the proteins that attach directly or indirectly on the surface of nanoparticles is quantified. These methods, however, do not always provide accurate or reliable results.
In this study, researchers hypothesized that by optimizing the particle dosage, species of blood matrix, and anticoagulants, they would be able to develop a set of conditions in vitro that correlated with previous in vivo findings and would allow efficient screening of nanomaterials.
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