光动力疗法（PDT）是一种有前景的肿瘤治疗方法，通过光诱导产生的活性氧（ROS）破坏DNA。然而，肿瘤细胞可以启动DNA修复途径以抵抗氧化性损伤。本研究基于报道的PARP1抑制剂rucaparib，开发了一种核定位光敏剂PARP-PS，具有多(ADP-核糖基)聚合酶1 (PARP1) 抑制活性。作为双模式的DNA损伤剂，PARP-PS能够在光照射下损伤DNA，并通过PARP1抑制和降解阻断DNA修复途径，增强氧化性DNA损伤。体外和体内研究均表明，PARP-PS在乳腺癌中具有高抗肿瘤活性，并只产生少量的副作用。此外，PARP-PS可作为免疫原性细胞死亡（ICD）诱导剂，激活免疫反应，促进细胞毒性T淋巴细胞激活和肿瘤浸润。因此，PARP-PS是一种具有协同光治疗、化疗和免疫疗法效应的多模式抗肿瘤剂。本文受版权保护。保留所有权利。

Photodynamic therapy (PDT) is a promising cancer therapeutic method that can damage DNA via photoinduced reactive oxygen species (ROS) production. However, tumor cells can initiate DNA repair pathways to resist oxidative damage. In this study, a nuclear-targeted photosensitizer PARP-PS with a poly (ADP-ribose) polymerase 1 (PARP1) inhibitory effect was developed based on the reported PARP1 inhibitor, rucaparib. As a dual-mode DNA-damaging agent, PARP-PS damages DNA upon photoirradiation and enhances oxidative DNA damage by blocking the DNA repair pathway via PARP1 inhibition and degradation. Both in vitro and in vivo investigations demonstrated that PARP-PS exhibits high antitumor activity with few side effects in breast cancer. In addition, PARP-PS can act as an immunogenic cell death (ICD) inducer to activate immune responses characterized by the promotion of cytotoxic T lymphocyte activation and tumor infiltration. Therefore, PARP-PS is a potential multimodal antitumor agent with synergistic phototherapeutic, chemotherapeutic, and immunotherapeutic effects. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.