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Peer-reviewedCC BYBioactive Materials

A fluorinated poly(amino acid) nanovaccine with spatiotemporally encoded innate priming and antigen cross-presentation for tumor immunotherapy

  • Zijuan Wang1
  • Yuanzhen Su1
  • Shucheng Zhang1
  • Bingzheng Yu1
  • Yan Wei2
  • Hao Liu2
  • Irina A. Veselova3
  • Shixian Lv4
4 affiliations
  1. 1Key Laboratory of Polymer Chemistry and Physics of Ministry of Education, School of Materials Science and Engineering, Peking University, Beijing, 100871, China
  2. 2Peking University School and Hospital of Stomatology, Peking University, Beijing, 100081, China
  3. 3Department of Chemistry, Lomonosov Moscow State University, Moscow, 119991, Russia
  4. 4Key Laboratory of Polymer Chemistry and Physics of Ministry of Education, School of Materials Science and Engineering, Peking University, Beijing, 100871, China; Corresponding author.
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Abstract

The efficacy of cancer vaccines depends on spatiotemporally coordinated innate immune priming and antigen cross-presentation, but this hierarchy remains difficult to control with existing delivery platforms. Here, we report a fluorinated diethylenetriamine-modified poly(aspartic acid) nanovaccine platform, termed DET-F, and identify DET-F30 as the optimized formulation for antigen delivery and immune activation. Perfluorooctyl side chains promote early endosomal toll-like receptor 3 (TLR3) associated innate immune signaling and dendritic cell maturation, whereas the pH-responsive polymer backbone facilitates subsequent endosomal escape and cytosolic antigen release. This chemically encoded sequence enables delayed yet enhanced antigen cross-presentation in mature dendritic cells. DET-F30/antigen nanoparticles display efficient antigen loading and cellular uptake, activate TLR3-related innate immune pathways, and elicit robust antigen-specific CD8 + T cell immunity. In multiple tumor models, DET-F30-based vaccination suppresses tumor growth and metastasis, prolongs survival, and enhances post-surgical anti-PD-1 therapy. This work establishes fluorinated poly(amino acid)s as minimalist self-adjuvant nanovaccine vectors and demonstrates that precise polymer-architecture encoding can orchestrate sequential innate immune activation and antigen processing for improved cancer immunotherapy.

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Cite

BibTeXRIS
BibTeX
@article{wang2026fluorinated,
  title = {{A fluorinated poly(amino acid) nanovaccine with spatiotemporally encoded innate priming and antigen cross-presentation for tumor immunotherapy}},
  author = {Zijuan Wang and Yuanzhen Su and Shucheng Zhang and Bingzheng Yu and Yan Wei and Hao Liu and Irina A. Veselova and Shixian Lv},
  journal = {Bioactive Materials},
  year = {2026},
  month = nov,
  doi = {10.1016/j.bioactmat.2026.10.034},
  url = {https://doi.org/10.1016/j.bioactmat.2026.10.034},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - A fluorinated poly(amino acid) nanovaccine with spatiotemporally encoded innate priming and antigen cross-presentation for tumor immunotherapy
AU  - Zijuan Wang
AU  - Yuanzhen Su
AU  - Shucheng Zhang
AU  - Bingzheng Yu
AU  - Yan Wei
AU  - Hao Liu
AU  - Irina A. Veselova
AU  - Shixian Lv
PY  - 2026
DA  - 2026/11/06
JO  - Bioactive Materials
DO  - 10.1016/j.bioactmat.2026.10.034
UR  - https://doi.org/10.1016/j.bioactmat.2026.10.034
AB  - The efficacy of cancer vaccines depends on spatiotemporally coordinated innate immune priming and antigen cross-presentation, but this hierarchy remains difficult to control with existing delivery platforms. Here, we report a fluorinated diethylenetriamine-modified poly(aspartic acid) nanovaccine platform, termed DET-F, and identify DET-F30 as the optimized formulation for antigen delivery and immune activation. Perfluorooctyl side chains promote early endosomal toll-like receptor 3 (TLR3) associated innate immune signaling and dendritic cell maturation, whereas the pH-responsive polymer backbone facilitates subsequent endosomal escape and cytosolic antigen release. This chemically encoded sequence enables delayed yet enhanced antigen cross-presentation in mature dendritic cells. DET-F30/antigen nanoparticles display efficient antigen loading and cellular uptake, activate TLR3-related innate immune pathways, and elicit robust antigen-specific CD8 + T cell immunity. In multiple tumor models, DET-F30-based vaccination suppresses tumor growth and metastasis, prolongs survival, and enhances post-surgical anti-PD-1 therapy. This work establishes fluorinated poly(amino acid)s as minimalist self-adjuvant nanovaccine vectors and demonstrates that precise polymer-architecture encoding can orchestrate sequential innate immune activation and antigen processing for improved cancer immunotherapy.
SN  - 2452-199X
ER  -