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Examining cellular responses to reconstituted antibody protein liquids

Protein ionic liquids (PIL) are a new class of biologic stabilizers designed to protect the functionality and extend the shelf-life of biotechnological and therapeutic agents making them more readily available, and resistant to austere environments. Protein biorecognition elements such as monoclonal...

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Autores principales: Nelson, M. Tyler, Slocik, Joseph M., Romer, Eric J., Mankus, Cassandra I., Agans, Richard T., Naik, Rajesh R., Hussain, Saber M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382709/
https://www.ncbi.nlm.nih.gov/pubmed/34426606
http://dx.doi.org/10.1038/s41598-021-96375-8
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author Nelson, M. Tyler
Slocik, Joseph M.
Romer, Eric J.
Mankus, Cassandra I.
Agans, Richard T.
Naik, Rajesh R.
Hussain, Saber M.
author_facet Nelson, M. Tyler
Slocik, Joseph M.
Romer, Eric J.
Mankus, Cassandra I.
Agans, Richard T.
Naik, Rajesh R.
Hussain, Saber M.
author_sort Nelson, M. Tyler
collection PubMed
description Protein ionic liquids (PIL) are a new class of biologic stabilizers designed to protect the functionality and extend the shelf-life of biotechnological and therapeutic agents making them more readily available, and resistant to austere environments. Protein biorecognition elements such as monoclonal antibodies are commonly utilized therapeutics that require the robust stabilization offered by PILs, but biocompatibility remains an important issue. This study has focused on characterizing the biocompatibility of an antibody based PIL by exposing multiple cells types to a cationized immunoglobulin suspended in an anionic liquid (IgG-IL). The IgG-IL caused no significant alterations in cellular health for all three cell types with treatments < 12.5 µg/mL. Concentrations ≥ 12.5 µg/mL resulted in significant necrotic cell death in A549 and HaCaT cells, and caspase associated cell death in HepG2 cells. In addition, all cells displayed evidence of oxidative stress and IL-8 induction in response to IgG-IL exposures. Therapeutic Ig can be utilized with a wide dose range that extends into concentrations we have found to exhibit cytotoxicity raising a toxicity concern and a need for more extensive understanding of the biocompatibility of IgG-ILs.
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spelling pubmed-83827092021-09-01 Examining cellular responses to reconstituted antibody protein liquids Nelson, M. Tyler Slocik, Joseph M. Romer, Eric J. Mankus, Cassandra I. Agans, Richard T. Naik, Rajesh R. Hussain, Saber M. Sci Rep Article Protein ionic liquids (PIL) are a new class of biologic stabilizers designed to protect the functionality and extend the shelf-life of biotechnological and therapeutic agents making them more readily available, and resistant to austere environments. Protein biorecognition elements such as monoclonal antibodies are commonly utilized therapeutics that require the robust stabilization offered by PILs, but biocompatibility remains an important issue. This study has focused on characterizing the biocompatibility of an antibody based PIL by exposing multiple cells types to a cationized immunoglobulin suspended in an anionic liquid (IgG-IL). The IgG-IL caused no significant alterations in cellular health for all three cell types with treatments < 12.5 µg/mL. Concentrations ≥ 12.5 µg/mL resulted in significant necrotic cell death in A549 and HaCaT cells, and caspase associated cell death in HepG2 cells. In addition, all cells displayed evidence of oxidative stress and IL-8 induction in response to IgG-IL exposures. Therapeutic Ig can be utilized with a wide dose range that extends into concentrations we have found to exhibit cytotoxicity raising a toxicity concern and a need for more extensive understanding of the biocompatibility of IgG-ILs. Nature Publishing Group UK 2021-08-23 /pmc/articles/PMC8382709/ /pubmed/34426606 http://dx.doi.org/10.1038/s41598-021-96375-8 Text en © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Nelson, M. Tyler
Slocik, Joseph M.
Romer, Eric J.
Mankus, Cassandra I.
Agans, Richard T.
Naik, Rajesh R.
Hussain, Saber M.
Examining cellular responses to reconstituted antibody protein liquids
title Examining cellular responses to reconstituted antibody protein liquids
title_full Examining cellular responses to reconstituted antibody protein liquids
title_fullStr Examining cellular responses to reconstituted antibody protein liquids
title_full_unstemmed Examining cellular responses to reconstituted antibody protein liquids
title_short Examining cellular responses to reconstituted antibody protein liquids
title_sort examining cellular responses to reconstituted antibody protein liquids
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382709/
https://www.ncbi.nlm.nih.gov/pubmed/34426606
http://dx.doi.org/10.1038/s41598-021-96375-8
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