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

Authors Francian A, Mann K, Kullberg M

Received 4 April 2017

Accepted for publication 2 June 2017

Published 19 July 2017 Volume 2017:12 Pages 5149—5161

DOI https://doi.org/10.2147/IJN.S138787

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Thomas Webster


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
 

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