Oxidized carbon nanoparticles as an effective protein antigen delivery system targeting the cell-mediated immune response

Pritsana Sawutdeechaikul1,2, Banphot Jiangchareon,3–5 Supason Wanichwecharungruang,3–6 Tanapat Palaga1–31Graduate Program in Microbiology and Microbial Technology, Department of Microbiology, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand; 2Center...

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Autores principales:	Sawutdeechaikul P, Jiangchareon B, Wanichwecharungruang S, Palaga T
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	Oxidize carbon nanosphere macrophages adjuvant cell-mediated immune response Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/91a8c2ac1a0046b995bc49b9ff895d6e
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spelling	oai:doaj.org-article:91a8c2ac1a0046b995bc49b9ff895d6e2021-12-02T07:46:29ZOxidized carbon nanoparticles as an effective protein antigen delivery system targeting the cell-mediated immune response1178-2013https://doaj.org/article/91a8c2ac1a0046b995bc49b9ff895d6e2019-07-01T00:00:00Zhttps://www.dovepress.com/oxidized-carbon-nanoparticles-as-an-effective-protein-antigen-delivery-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Pritsana Sawutdeechaikul1,2, Banphot Jiangchareon,3–5 Supason Wanichwecharungruang,3–6 Tanapat Palaga1–31Graduate Program in Microbiology and Microbial Technology, Department of Microbiology, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand; 2Center of Excellence in Immune-mediated Diseases, Chulalongkorn University, Bangkok 10330, Thailand; 3Center of Excellence in Materials and Bio-Interfaces, Chulalongkorn University, Bangkok, 10330, Thailand; 4Nanotec-CU Center of Excellence on Food and Agriculture, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand; 5Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand; 6Center of Excellence on Petrochemical and Materials Technology, Chulalongkorn University, Bangkok, 10330, ThailandBackground: The demand for an effective vaccine delivery system that drives a suitable immune response is increasing. The oxidized carbon nanosphere (OCN), a negatively charged carbon nanoparticle, has the potential to fulfill this requirement because it can efficiently deliver macromolecules into cells and allows endosomal leakage. However, fundamental insights into how OCNs are taken up by antigen-presenting cells, and the intracellular behavior of delivered molecules is lacking. Furthermore, how immune responses are stimulated by OCN-mediated delivery has not been investigated.Purpose: In this study, the model protein antigen ovalbumin (OVA) was used to investigate the uptake mechanism and intracellular fate of OCN-mediated delivery of protein in macrophages. Moreover, the immune response triggered by OVA delivered by OCNs was characterized.Methods: Bone-marrow-derived macrophages (BMDMs) from mice were used to study antigen uptake and intracellular trafficking. Mice were immunized using OCN–OVA combined with known adjuvants, and the specific immune response was measured.Results: OCNs showed no cytotoxicity against BMDMs. OCN-mediated delivery of OVA into BMDMs was partially temperature independent process. Using specific inhibitors, it was revealed that intracellular delivery of OCN–OVA does not rely on phagocytosis or the clathrin- and lipid raft/caveolae-mediated pathways. Delivered OVA was found to colocalize with compartments containing MHC class I, but not with early endosomes, lysosomes, and autophagosomes. Immunization of OVA using OCNs in combination with the known adjuvant monophosphoryl lipid A specifically enhanced interferon gamma (IFNγ)- and granzyme B-producing cytotoxic T cells (CTLs).Conclusion: OCNs effectively delivered protein antigens into macrophages that localized with compartments containing MHC class I partially by the temperature independent, but not clathrin- and lipid raft/caveolae-mediated pathways. Increased CD8+, T-cell activity was induced by OCN-delivered antigens, suggesting antigen processing toward antigen presentation for CTLs. Taken together, OCNs are a potential protein antigen delivery system that stimulates the cell-mediated immune response.Keywords: oxidized carbon nanosphere, macrophages, adjuvant, cell-mediated immune responseSawutdeechaikul PJiangchareon BWanichwecharungruang SPalaga TDove Medical PressarticleOxidize carbon nanospheremacrophagesadjuvantcell-mediated immune responseMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 4867-4880 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Oxidize carbon nanosphere macrophages adjuvant cell-mediated immune response Medicine (General) R5-920
spellingShingle	Oxidize carbon nanosphere macrophages adjuvant cell-mediated immune response Medicine (General) R5-920 Sawutdeechaikul P Jiangchareon B Wanichwecharungruang S Palaga T Oxidized carbon nanoparticles as an effective protein antigen delivery system targeting the cell-mediated immune response
description	Pritsana Sawutdeechaikul1,2, Banphot Jiangchareon,3–5 Supason Wanichwecharungruang,3–6 Tanapat Palaga1–31Graduate Program in Microbiology and Microbial Technology, Department of Microbiology, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand; 2Center of Excellence in Immune-mediated Diseases, Chulalongkorn University, Bangkok 10330, Thailand; 3Center of Excellence in Materials and Bio-Interfaces, Chulalongkorn University, Bangkok, 10330, Thailand; 4Nanotec-CU Center of Excellence on Food and Agriculture, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand; 5Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand; 6Center of Excellence on Petrochemical and Materials Technology, Chulalongkorn University, Bangkok, 10330, ThailandBackground: The demand for an effective vaccine delivery system that drives a suitable immune response is increasing. The oxidized carbon nanosphere (OCN), a negatively charged carbon nanoparticle, has the potential to fulfill this requirement because it can efficiently deliver macromolecules into cells and allows endosomal leakage. However, fundamental insights into how OCNs are taken up by antigen-presenting cells, and the intracellular behavior of delivered molecules is lacking. Furthermore, how immune responses are stimulated by OCN-mediated delivery has not been investigated.Purpose: In this study, the model protein antigen ovalbumin (OVA) was used to investigate the uptake mechanism and intracellular fate of OCN-mediated delivery of protein in macrophages. Moreover, the immune response triggered by OVA delivered by OCNs was characterized.Methods: Bone-marrow-derived macrophages (BMDMs) from mice were used to study antigen uptake and intracellular trafficking. Mice were immunized using OCN–OVA combined with known adjuvants, and the specific immune response was measured.Results: OCNs showed no cytotoxicity against BMDMs. OCN-mediated delivery of OVA into BMDMs was partially temperature independent process. Using specific inhibitors, it was revealed that intracellular delivery of OCN–OVA does not rely on phagocytosis or the clathrin- and lipid raft/caveolae-mediated pathways. Delivered OVA was found to colocalize with compartments containing MHC class I, but not with early endosomes, lysosomes, and autophagosomes. Immunization of OVA using OCNs in combination with the known adjuvant monophosphoryl lipid A specifically enhanced interferon gamma (IFNγ)- and granzyme B-producing cytotoxic T cells (CTLs).Conclusion: OCNs effectively delivered protein antigens into macrophages that localized with compartments containing MHC class I partially by the temperature independent, but not clathrin- and lipid raft/caveolae-mediated pathways. Increased CD8+, T-cell activity was induced by OCN-delivered antigens, suggesting antigen processing toward antigen presentation for CTLs. Taken together, OCNs are a potential protein antigen delivery system that stimulates the cell-mediated immune response.Keywords: oxidized carbon nanosphere, macrophages, adjuvant, cell-mediated immune response
format	article
author	Sawutdeechaikul P Jiangchareon B Wanichwecharungruang S Palaga T
author_facet	Sawutdeechaikul P Jiangchareon B Wanichwecharungruang S Palaga T
author_sort	Sawutdeechaikul P
title	Oxidized carbon nanoparticles as an effective protein antigen delivery system targeting the cell-mediated immune response
title_short	Oxidized carbon nanoparticles as an effective protein antigen delivery system targeting the cell-mediated immune response
title_full	Oxidized carbon nanoparticles as an effective protein antigen delivery system targeting the cell-mediated immune response
title_fullStr	Oxidized carbon nanoparticles as an effective protein antigen delivery system targeting the cell-mediated immune response
title_full_unstemmed	Oxidized carbon nanoparticles as an effective protein antigen delivery system targeting the cell-mediated immune response
title_sort	oxidized carbon nanoparticles as an effective protein antigen delivery system targeting the cell-mediated immune response
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/91a8c2ac1a0046b995bc49b9ff895d6e
work_keys_str_mv	AT sawutdeechaikulp oxidizedcarbonnanoparticlesasaneffectiveproteinantigendeliverysystemtargetingthecellmediatedimmuneresponse AT jiangchareonb oxidizedcarbonnanoparticlesasaneffectiveproteinantigendeliverysystemtargetingthecellmediatedimmuneresponse AT wanichwecharungruangs oxidizedcarbonnanoparticlesasaneffectiveproteinantigendeliverysystemtargetingthecellmediatedimmuneresponse AT palagat oxidizedcarbonnanoparticlesasaneffectiveproteinantigendeliverysystemtargetingthecellmediatedimmuneresponse
_version_	1718399171243802624

Oxidized carbon nanoparticles as an effective protein antigen delivery system targeting the cell-mediated immune response

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