Complement C3-dependent uptake of targeted liposomes into human macrophages, B cells, dendritic cells, neutrophils, and MDSCs

Alexandra Francian,1 Kristine Mann,1,2 Max Kullberg1 1WWAMI Medical Education Program, 2Department of Biological Sciences, University of Alaska Anchorage, Anchorage, AK, USA Abstract: Antitumor immunity in cancer patients is heavily modulated by cells of the innate immune system. Antigen-presentin...

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Autores principales: Francian A, Mann K, Kullberg M
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Lenguaje:EN
Publicado: Dove Medical Press 2017
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spelling oai:doaj.org-article:f36cd28b9b71492689827efdd7a445272021-12-02T01:08:05ZComplement C3-dependent uptake of targeted liposomes into human macrophages, B cells, dendritic cells, neutrophils, and MDSCs1178-2013https://doaj.org/article/f36cd28b9b71492689827efdd7a445272017-07-01T00:00:00Zhttps://www.dovepress.com/complement-c3-dependent-uptake-of-targeted-liposomes-into-human-macrop-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Alexandra Francian,1 Kristine Mann,1,2 Max Kullberg1 1WWAMI Medical Education Program, 2Department of Biological Sciences, University of Alaska Anchorage, Anchorage, AK, USA Abstract: Antitumor immunity in cancer patients is heavily modulated by cells of the innate immune system. Antigen-presenting cells, including dendritic cells, macrophages, and B cells, initiate immune recognition of tumor antigen by displaying antigen to effector cells. Countering this immune stimulation are immunosuppressive cells which include M2 macrophages, N2 neutrophils, and myeloid-derived suppressor cells (MDSCs). To create effective cancer immunotherapies, it is critical that we can target these important cell types of the immune system with immunostimulatory compounds. A commonality of these cell types is the complement receptor, which recognizes pathogens that are bound to activated complement C3 in human blood. To target the complement receptor, we have created a liposome that has a small molecule, orthopyridyl disulfide (OPSS), conjugated to its surface. OPSS forms a disulfide bond with activated complement C3, which then targets liposomes for uptake by dendritic cells, macrophages, B cells, MDSCs, and neutrophils in human blood. Internalization is efficient and specific to cells that display the complement receptor. Liposomes are a versatile drug delivery device. Possible applications for this system include delivery of toll-receptor agonists or tumor antigen to antigen-presenting cells and delivery of immunostimulatory drugs to M2, N2, and MDSC immunosuppressive cells. Keywords: cancer immuno therapy, antigen-presenting cells, complement C3, nanoparticle, targeted delivery Francian AMann KKullberg MDove Medical PressarticleCancer immunotherapyAntigen Presenting CellsComplement C3NanoparticleTargeted DeliveryMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 5149-5161 (2017)
institution DOAJ
collection DOAJ
language EN
topic Cancer immunotherapy
Antigen Presenting Cells
Complement C3
Nanoparticle
Targeted Delivery
Medicine (General)
R5-920
spellingShingle Cancer immunotherapy
Antigen Presenting Cells
Complement C3
Nanoparticle
Targeted Delivery
Medicine (General)
R5-920
Francian A
Mann K
Kullberg M
Complement C3-dependent uptake of targeted liposomes into human macrophages, B cells, dendritic cells, neutrophils, and MDSCs
description Alexandra Francian,1 Kristine Mann,1,2 Max Kullberg1 1WWAMI Medical Education Program, 2Department of Biological Sciences, University of Alaska Anchorage, Anchorage, AK, USA Abstract: Antitumor immunity in cancer patients is heavily modulated by cells of the innate immune system. Antigen-presenting cells, including dendritic cells, macrophages, and B cells, initiate immune recognition of tumor antigen by displaying antigen to effector cells. Countering this immune stimulation are immunosuppressive cells which include M2 macrophages, N2 neutrophils, and myeloid-derived suppressor cells (MDSCs). To create effective cancer immunotherapies, it is critical that we can target these important cell types of the immune system with immunostimulatory compounds. A commonality of these cell types is the complement receptor, which recognizes pathogens that are bound to activated complement C3 in human blood. To target the complement receptor, we have created a liposome that has a small molecule, orthopyridyl disulfide (OPSS), conjugated to its surface. OPSS forms a disulfide bond with activated complement C3, which then targets liposomes for uptake by dendritic cells, macrophages, B cells, MDSCs, and neutrophils in human blood. Internalization is efficient and specific to cells that display the complement receptor. Liposomes are a versatile drug delivery device. Possible applications for this system include delivery of toll-receptor agonists or tumor antigen to antigen-presenting cells and delivery of immunostimulatory drugs to M2, N2, and MDSC immunosuppressive cells. Keywords: cancer immuno therapy, antigen-presenting cells, complement C3, nanoparticle, targeted delivery 
format article
author Francian A
Mann K
Kullberg M
author_facet Francian A
Mann K
Kullberg M
author_sort Francian A
title Complement C3-dependent uptake of targeted liposomes into human macrophages, B cells, dendritic cells, neutrophils, and MDSCs
title_short Complement C3-dependent uptake of targeted liposomes into human macrophages, B cells, dendritic cells, neutrophils, and MDSCs
title_full Complement C3-dependent uptake of targeted liposomes into human macrophages, B cells, dendritic cells, neutrophils, and MDSCs
title_fullStr Complement C3-dependent uptake of targeted liposomes into human macrophages, B cells, dendritic cells, neutrophils, and MDSCs
title_full_unstemmed Complement C3-dependent uptake of targeted liposomes into human macrophages, B cells, dendritic cells, neutrophils, and MDSCs
title_sort complement c3-dependent uptake of targeted liposomes into human macrophages, b cells, dendritic cells, neutrophils, and mdscs
publisher Dove Medical Press
publishDate 2017
url https://doaj.org/article/f36cd28b9b71492689827efdd7a44527
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AT mannk complementc3dependentuptakeoftargetedliposomesintohumanmacrophagesbcellsdendriticcellsneutrophilsandmdscs
AT kullbergm complementc3dependentuptakeoftargetedliposomesintohumanmacrophagesbcellsdendriticcellsneutrophilsandmdscs
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