Functionalization promotes pathogen-mimicking characteristics of polyanhydride nanoparticle adjuvants

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

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Rational design of adjuvants and delivery systems will promote development of next-generation vaccines to control emerging and re-emerging diseases. To accomplish this, understanding the immune-enhancing properties of new adjuvants relative to those induced by natural infections can help with the development of pathogen-mimicking materials that will effectively initiate innate immune signaling cascades. In this work, the surfaces of polyanhydride nanoparticles composed of sebacic acid (SA) and 1,6-bis(p-carboxyphenoxy) hexane were decorated with an ethylene diamine spacer partially modified with either a glycolic acid linker or an α-1,2-linked di-mannopyranoside (di-mannose) to confer “pathogen-like” properties and enhance adjuvanticity. Co-incubation of linker-modified nanoparticles with dendritic cells (DCs) elicited significant increases in surface expression of MHC I, MHC II, CD86, and CD40, and enhanced secretion of IL-6, IL-12p40, and TNF-α. An 800% increase in uptake of ethylene-diamine-spaced, linker and di-mannose functionalized polyanhydride nanoparticles was also observed. Together, our data showed that linker-functionalized polyanhydride nanoparticles demonstrate similar patterns of uptake, intracellular trafficking, particle persistence, and innate activation as did DCs exposed to Yersinia pestis or Escherichia coli. These results set the stage for rational selection of adjuvant chemistries to induce pathogen-mimicking immune responses.

Original languageEnglish (US)
Pages (from-to)2762-2771
Number of pages10
JournalJournal of Biomedical Materials Research - Part A
Volume105
Issue number10
DOIs
StatePublished - Oct 2017

Keywords

  • nanoparticles
  • pathogen-mimicking
  • polyanhydride
  • targeted vaccines
  • uptake

ASJC Scopus subject areas

  • Ceramics and Composites
  • Biomaterials
  • Biomedical Engineering
  • Metals and Alloys

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    Phanse, Y., Carrillo-Conde, B. R., Ramer-Tait, A. E., Roychoudhury, R., Broderick, S., Pohl, N., Rajan, K., Narasimhan, B., Wannemuehler, M. J., & Bellaire, B. H. (2017). Functionalization promotes pathogen-mimicking characteristics of polyanhydride nanoparticle adjuvants. Journal of Biomedical Materials Research - Part A, 105(10), 2762-2771. https://doi.org/10.1002/jbm.a.36128