Functionalization of polyanhydride microparticles with di-mannose influences uptake by and intracellular fate within dendritic cells

Yashdeep Phanse, Brenda R. Carrillo-Conde, Amanda E. Ramer-Tait, Rajarshi Roychoudhury, Nicola L.B. Pohl, Balaji Narasimhan, Michael J. Wannemuehler, Bryan H. Bellaire

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)8902-8909
Number of pages8
JournalActa Biomaterialia
Volume9
Issue number11
DOIs
StatePublished - Nov 2013

Keywords

  • C-type lectin receptors
  • Di-mannose
  • Microparticles
  • Polyanhydride
  • Targeted vaccines
  • Uptake

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Biochemistry
  • Biomedical Engineering
  • Molecular Biology

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