Multivalent nanomaterials: Learning from vaccines and progressing to antigen-specific immunotherapies

Brittany L. Hartwell, Lorena Antunez, Bradley P. Sullivan, Sharadvi Thati, Joshua O. Sestak, Cory Berkland

Research output: Contribution to journalReview articlepeer-review

39 Scopus citations

Abstract

Continued development of multivalent nanomaterials has provided opportunities for the advancement of antigen-specific immunotherapies. New insights emerge when considering the backdrop of vaccine design, which has long employed multivalent presentation of antigen to more strongly engage and enhance an immunogenic response. Additionally, vaccines traditionally codeliver antigen with adjuvant to amplify a robust antigen-specific response. Multivalent nanomaterials have since evolved for applications where immune tolerance is desired, such as autoimmune diseases or allergies. In particular, soluble, linear polymers may be tailored to direct antigen-specific immunogenicity or tolerance by modulating polymer length, ligand valency (number), and ligand density, in addition to incorporating secondary signals. Codelivery of a secondary signal may direct, amplify, or suppress the response to a given antigen. Although the ability of multivalent nanomaterials to enact an immune response through molecular mechanisms has been established, a transport mechanism for biodistribution must also be considered. Both mechanisms are influenced by ligand display and other physical properties of the nanomaterial. This review highlights multivalent ligand display on linear polymers, the complex interplay of physical parameters in multivalent design, and the ability to direct the immune response by molecular and transport mechanisms.

Original languageEnglish (US)
Pages (from-to)346-361
Number of pages16
JournalJournal of Pharmaceutical Sciences
Volume104
Issue number2
DOIs
StatePublished - Feb 2015
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Keywords

  • Immune response
  • Immunotherapy
  • Multivalency
  • Nanoparticles
  • Pharmacokinetics
  • Polymeric drug delivery systems
  • Receptor clustering
  • Targeted drug delivery
  • Transport
  • Vaccines

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