A Tumor‐Microenvironment‐Activatable Molecular Pro‐Theranostic Agent for Photodynamic and Immunotherapy of Cancer

• Published in: Advanced materials (Weinheim) 2023-07, Vol.35 (30), p.e2211485-n/a
• Main Authors: Zhou, Hui, Zhang, Yuan, Zhang, Ruru, Zhao, Min, Chen, Wan, Liu, Yinghua, Jiang, Yue, Li, Qing, Miao, Qingqing, Gao, Mingyuan
• Format: Article
• Language: English
• Subjects: Cancer; cancer‐associated fibroblasts; Cell death; fibroblast activation protein α; Fibroblasts; Immunosuppression; Immunotherapy; Materials science; Medical imaging; photodynamic therapy; theranostics; Tumors
• ISSN: 0935-9648; 1521-4095
• DOI: 10.1002/adma.202211485

Cancer‐associated fibroblasts (CAFs) are the major components of the tumor‐associated matrix and play an important role in tumor progression and immunosuppression. Therefore, precise theranostics of CAFs are beneficial for CAFs‐targeted therapies. However, imaging agents enabling precise theranostics of CAFs have been rarely exploited. To tackle this issue, a molecular pro‐theranostic probe (FMP) with activatable fluorescence, photoacoustic (PA) imaging, and photodynamic therapy (PDT) is developed in response to fibroblast activation protein α (FAPα) overexpressed in >90% types of CAFs and some tumor cells. Attributed to efficient activatable phototoxicity toward CAFs and tumor cells, together with activated immunogenic cell death (ICD), complete tumor regression of primary tumors and abscopal effect of distant tumors are observed in a 4T1‐tumor‐bearing mice model. By integration with PD‐L1 checkpoint blockade immunotherapy, enhanced systemic immune responses are evoked to obtain long‐lasting tumor suppression of both primary and distant tumors as well as arrest systemic cancer metastasis in living mice. A fibroblast activation protein α (FAPα)‐activatable pro‐theranostic probe (FMP) has activated fluorescence and photoacoustic‐imaging‐guided photodynamic therapy immunotherapy for the simultaneous killing of cancer‐associated fibroblasts (CAFs) and cancer cells. FMP‐mediated immunotherapy can not only improve tumor immunogenicity, but also exhaust CAFs, promote cytotoxic T lymphocytes and aPD‐L1 to enter the CAF‐rich tumors, thus strengthening the synergistic antitumor immune response.