Polymer–Protein Nanovaccine Synthesized via Reactive Self-Assembly with Potential Application in Cancer Immunotherapy: Physicochemical and Biological Characterization In Vitro and In Vivo

Mingming Zhang, Wenjuan Chen, Yuanyuan Ju, Hanying Zhao, Chun Wang

Research output: Contribution to journalArticlepeer-review

Abstract

Nanovaccines composed of polymeric nanocarriers and protein-based antigens have attracted much attention in recent years because of their enormous potential in the prevention and treatment of diseases such as viral infections and cancer. While surface-conjugated protein antigens are known to be more immunoactive than encapsulated antigens, current surface conjugation methods often result in low and insufficient protein loading. Herein, reactive self-assembly is used to prepare nanovaccine from poly(ε-caprolactone) (PCL) and ovalbumin (OVA)—a model antigen. A rapid thiol-disulfide exchange reaction between PCL with pendant pyridyl disulfide groups and thiolated OVA results in the formation of nanoparticles with narrow size distribution. High OVA loading (≈70–80 wt%) is achieved, and the native secondary structure of OVA is preserved. Compared to free OVA, the nanovaccine is much superior in enhancing antigen uptake by bone marrow-derived dendritic cells (BMDCs), promoting BMDC maturation and antigen presentation via the MHC I pathway, persisting at the injection site and draining lymph nodes, activating both Th1 and Th2 T cell immunity, and ultimately, resisting tumor challenge in mice. This is the first demonstration of reactive self-assembly for the construction of a polymer–protein nanovaccine with clear potential in advancing cancer immunotherapy.

Original languageEnglish (US)
Article number2300438
JournalMacromolecular Rapid Communications
Volume44
Issue number23
DOIs
StatePublished - Dec 2023
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2023 The Authors. Macromolecular Rapid Communications published by Wiley-VCH GmbH.

Keywords

  • cancers
  • immunotherapy
  • nanovaccines
  • polymer–protein conjugation
  • reactive self-assembly

PubMed: MeSH publication types

  • Journal Article

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