癌细胞装备丰富的抗氧化剂，如谷胱甘肽（GSH），以消除反应性氧化物种（ROS），从而降低光动力治疗（PDT）的治疗效果。 PDT中的另一个挑战是规避PDT诱导的缺氧情况，这引起了血管内皮生长因子（VEGF）等促血管生成因子的上调。 因此，可以通过同时传递具有GSH耗竭剂和VEGF抑制剂的光敏剂来最大限度地提高PDT的治疗效果。 为了实现PDT与原位GSH耗竭和VEGF抑制的合作治疗作用，我们开发了肿瘤靶向氧化还原调节和抗血管生成的光治疗纳米组装体（tRAPs），由自组装二硫化物桥连的硼苯甲酸酯（ssBR），光敏剂（IR780）和肿瘤靶向明胶组成。 tRAPs的框架被理性设计成形成纳米构造体，作为光敏剂载体，具有固有的GSH耗竭和VEGF抑制能力。 tRAPs有效地降低了细胞内GSH，使癌细胞对ROS更加脆弱，并在近红外光（NIR）激光照射下引起了癌细胞的免疫原性细胞死亡（ICD）。 在小鼠异种移植模型中，tRAPs优先积聚在肿瘤中，并在激光照射下显著根除了肿瘤。 tRAPs的设计理念提供了一种简单而通用的策略，可用于开发具有极高潜力的自我增强光治疗剂以用于靶向癌症治疗。 版权所有©2023 Elsevier Ltd。保留所有权利。

Cancer cells are equipped with abundant antioxidants such as glutathione (GSH) that eliminate reactive oxygen species (ROS) to deteriorate the therapeutic efficacy of photodynamic therapy (PDT). Another challenge in PDT is circumventing PDT-induced hypoxic condition that provokes upregulation of pro-angiogenic factor such as vascular endothelial growth factor (VEGF). It is therefore reasonable to expect that therapeutic outcomes of PDT could be maximized by concurrent delivery of photosensitizers with GSH depleting agents and VEGF suppressors. To achieve cooperative therapeutic actions of PDT with in situ GSH depletion and VEGF suppression, we developed tumor targeted redox-regulating and antiangiogenic phototherapeutic nanoassemblies (tRAPs) composed of self-assembling disulfide-bridged borylbenzyl carbonate (ssBR), photosensitizer (IR780) and tumor targeting gelatin. As a framework of tRAPs, ssBR was rationally designed to form nanoconstructs that serve as photosensitizer carriers with intrinsic GSH depleting- and VEGF suppressing ability. tRAPs effectively depleted intracellular GSH to render cancer cells more vulnerable to ROS and also provoked immunogenic cell death (ICD) of cancer cells upon near infrared (NIR) laser irradiation. In mouse xenograft models, tRAPs preferentially accumulated in tumors and dramatically eradicated tumors with laser irradiation. The design rationale of tRAPs provides a simple and versatile strategy to develop self-boosting phototherapeutic agents with great potential in targeted cancer therapy.Copyright © 2023 Elsevier Ltd. All rights reserved.