癌相关成纤维细胞（CAFs）是肿瘤相关基质的主要成分，对肿瘤进展和免疫抑制起重要作用。因此，精确的CAFs治疗诊断对CAFs靶向治疗非常有益。但是，能够实现精确的CAF治疗诊断的成像剂很少被利用。为了解决这个问题，我们开发了一种分子前疗法探针（FMP），具有可活化荧光、光声（PA）成像和光动力学治疗（PDT），并针对Fibroblast Activation Protein α（FAPα）进行响应，该蛋白在90％以上类型的CAFs和某些肿瘤细胞中过度表达。由于对CAFs和肿瘤细胞的高效可活化光毒性以及激活的免疫原性细胞死亡（ICD），在4T1肿瘤携带的小鼠模型中观察到原发性肿瘤的完全肿瘤消退和远处肿瘤的脱离效应。通过与PD-L1检查点阻断免疫疗法的整合，已经激发了增强的全身免疫反应，以获得原发性和远处肿瘤的长期抑制以及阻止活体小鼠的全身癌转移。本文受版权保护。版权所有。

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 to CAFs-targeted therapies. However, imaging agents enabling precise theranostics of CAFs have been rarely exploited. To tackle this issue, we develop a molecular pro-theranostic probe (FMP) with activatable fluorescence, photoacoustic (PA) imaging, and photodynamic therapy (PDT) in response to fibroblast activation protein α (FAPα) overexpressed in more than 90% types of CAFs and some tumor cells. Attributing to efficient activatable photo-toxicity towards 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 on the 4T1 tumor-bearing mice model. By integration with PD-L1 checkpoint blockade immunotherapy, enhanced systemic immune responses have been evoked to obtain long-lasting tumor suppression of both primary and distant tumors as well as arrest systemic cancer metastasis in living mice. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.