Journal
ACTA BIOMATERIALIA
Volume 9, Issue 11, Pages 8902-8909Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2013.06.024
Keywords
Polyanhydride; Microparticles; C-type lectin receptors; Uptake; Targeted vaccines; Di-mannose
Funding
- US Department of Defense - Office of Naval Research (ONR) [N00014-06-1-1176]
- US Army Medical Research and Materiel Command [W81XWH-10-1-0806]
- Iowa State University College of Veterinary Medicine and the Office of Biotechnology
- Health Resources and Services Administration [C76HF19578]
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Innovative vaccine delivery platforms can facilitate the development of effective single-dose treatment regimens to control emerging and re-emerging infectious diseases. Polyanhydride microparticles are promising vaccine delivery vehicles due to their ability to stably maintain antigens, provide tailored release kinetics and function as adjuvants. A major obstacle for the use of microparticle-based vaccines, however, is their limited uptake by dendritic cells (DCs). In this study, we functionalized the microparticle surface with di-mannose in order to target C-type lectin receptors (CLRs) on DCs. Polyanhydride particles based on sebacic acid (SA), 1,6-bis(p-carboxyphenoxy)hexane (CPH) and 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG) were evaluated. Co-incubation of di-mannose-functionalized microparticles up-regulated the expression of CLRs on DCs. More importantly, di-mannose functionalization increased the uptake, as measured by the percentage of cells internalizing particles. The uptake of CPH:SA microparticles increased similar to 20-fold, from 0.82% (non-functionalized) to 20.2%, and internalization of CPTEG:CPH microparticles increased similar to 7-fold from 1.35% (non-functionalized) to 9.3% upon di-mannose functionalization. Both di-mannose-functionalized and non-functionalized particles trafficked to lysosomes. Together, these studies demonstrate that employing rational vaccine design principles, such as the targeting of CLRs on antigen-presenting cells, can enhance delivery of encapsulated antigens and potentially induce a more robust adaptive immune response. (C) 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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