FAP-Targeted Photodynamic Therapy Mediated by Ferritin Nanoparticles Elicits an Immune Response against Cancer Cells and Cancer Associated Fibroblasts

Shiyi Zhou, Zipeng Zhen, Amy V. Paschall, Lijun Xue, Xueyuan Yang, Anne Gaelle Bebin Blackwell, Zhengwei Cao, Weizhong Zhang, Mengzhe Wang, Yong Teng, Gang Zhou, Zibo Li, Fikri Y. Avci, Wei Tang, Jin Xie

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Cancer-associated fibroblasts (CAFs) are present in many types of tumors and play a pivotal role in tumor progression and immunosuppression. Fibroblast-activation protein (FAP), which is overexpressed on CAFs, has been indicated as a universal tumor target. However, FAP expression is not restricted to tumors, and systemic treatment against FAP often causes severe side effects. To solve this problem, a photodynamic therapy (PDT) approach is developed based on ZnF16Pc-loaded and FAP-specific single chain variable fragment (scFv)-conjugated apoferritin nanoparticles, or αFAP-Z@FRT. αFAP-Z@FRT PDT efficiently eradicates CAFs in tumors without inducing systemic toxicity. When tested in murine 4T1 models, the treatment elicits anti-cancer immunity, causing suppression of both primary and distant tumors, that is, the abscopal effect. Treatment efficacy is enhanced when αFAP-Z@FRT PDT is used in combination with anti-PD1 antibodies. Interestingly, it is found that the PDT treatment not only elicits a cellular immunity against cancer cells, but also stimulates an anti-CAFs immunity. This is supported by an adoptive cell transfer study, where T cells taken from 4T1-tumor-bearing animals treated with αFAP PDT retard the growth of A549 tumors established on nude mice. Overall, this approach is unique for permitting site-specific eradication of CAFs and inducing a broad spectrum anti-cancer immunity.

Original languageEnglish (US)
Article number2007017
JournalAdvanced Functional Materials
Volume31
Issue number7
DOIs
StatePublished - Feb 10 2021

Keywords

  • cancer associated fibroblast
  • fibroblast activation protein
  • immunomodulation
  • immunotherapy
  • photodynamic therapy

ASJC Scopus subject areas

  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics

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