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Functionalization of polyanhydride microparticles with di-mannose influences uptake by and intracellular fate within dendritic cells.
- Source :
-
Acta biomaterialia [Acta Biomater] 2013 Nov; Vol. 9 (11), pp. 8902-9. Date of Electronic Publication: 2013 Jun 22. - Publication Year :
- 2013
-
Abstract
- 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 ∼20-fold, from 0.82% (non-functionalized) to 20.2%, and internalization of CPTEG:CPH microparticles increased ∼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.<br /> (Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Endocytosis
Lectins, C-Type deficiency
Lectins, C-Type metabolism
Lysosomes metabolism
Mannose Receptor
Mannose-Binding Lectins deficiency
Mannose-Binding Lectins metabolism
Mice
Mice, Inbred C57BL
Photoelectron Spectroscopy
Polymers chemistry
Receptors, Cell Surface deficiency
Receptors, Cell Surface metabolism
Dendritic Cells cytology
Dendritic Cells metabolism
Disaccharides chemistry
Intracellular Space metabolism
Mannose chemistry
Microspheres
Polyanhydrides chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1878-7568
- Volume :
- 9
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Acta biomaterialia
- Publication Type :
- Academic Journal
- Accession number :
- 23796408
- Full Text :
- https://doi.org/10.1016/j.actbio.2013.06.024