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

• Published in: Advanced functional materials 2021-02, Vol.31 (7), p.n/a
• Main Authors: Zhou, Shiyi, Zhen, Zipeng, Paschall, Amy V., Xue, Lijun, Yang, Xueyuan, Bebin Blackwell, Anne‐Gaelle, Cao, Zhengwei, Zhang, Weizhong, Wang, Mengzhe, Teng, Yong, Zhou, Gang, Li, Zibo, Avci, Fikri Y., Tang, Wei, Xie, Jin
• Format: Article
• Language: English
• Subjects: Antibodies; Cancer; cancer associated fibroblast; Ferritin; fibroblast activation protein; Fibroblasts; Immune system; Immunity; immunomodulation; Immunosuppression; immunotherapy; Lymphocytes; Materials science; Nanoparticles; Photodynamic therapy; Side effects; Toxicity testing; Tumors
• ISSN: 1616-301X; 1616-3028
• DOI: 10.1002/adfm.202007017

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. Anti‐FAP photodynamic therapy, mediated by ZnF16Pc‐loaded and single‐chain variable‐fragment (scFv)‐conjugated ferritin nanoparticles, eliminates cancer associated fibroblasts (CAFs) in a specific fashion. This results in destructed extracellular matrix and reduced recruitment of regulatory T cells. In turn, the treatment enhances the expansion of anti‐cancer and anti‐CAF cytotoxic T lymphocytes, eliciting an immunity that inhibits tumor growth.