光动力疗法（PDT）是一种有前景的癌症治疗方法。然而，光敏剂（PSs）相对较短的肿瘤滞留时间使得难以抓住最佳治疗时机，并限制了在单次注射中进行多次PDT。本研究开发了一种肿瘤特异性光治疗纳米药物（DPPa NP），用于光动力/化疗联合治疗并延长PDT治疗窗口。DPPa NP通过将亲水性的氧化牛血清白蛋白（BSA-SOH）可结合的光敏剂DPPa与两亲性H2 O2 活化的氯麦比胺（CL）前药mPEG-TK-CL封装而成。这种设计使得在H2 O2 治疗下同时释放CL和DPPa。释放的CL不仅可以杀死肿瘤细胞，还可以提高肿瘤细胞内活性氧化物（ROS）水平，导致载荷的几乎完全释放。释放的DPPa可以与过表达的BSA-SOH结合，导致荧光信号恢复，该信号可用作CL释放和光动力效应的指示剂。更重要的是，这种结合将DPPa从小分子光敏剂转变为具有较长肿瘤滞留时间和PDT治疗窗口的大分子光敏剂，使得多次PDT成为可能。因此，本研究提供了一种延长PDT治疗窗口并实现肿瘤特异性荧光成像引导联合治疗的有效策略。本文受版权保护，图片和文字未经许可不得转载。

Photodynamic therapy (PDT) is a promising approach for cancer therapy. However, the relatively short tumor retention time of photosensitizers (PSs) makes it difficult to catch the optimal treatment time and restricts multiple PDT within single injection. In this study, a tumor-specific phototheranostic nanomedicine (DPPa NP) is developed for photodynamic/chemo combination therapy with prolonged PDT treatment window. DPPa NP is prepared via encapsulating a hydrophobic oxidized bovine serum albumin (BSA-SOH)-conjugatable photosensitizer DPPa with an amphiphilic H2 O2 -activatable chlorambucil (CL) prodrug mPEG-TK-CL. Such a design enables simultaneous release of CL and DPPa under the treatment of H2 O2 . The released CL can not only kill tumor cells, but also upregulate reactive oxygen species (ROS) level within tumor cells, leading to the almost fully release of cargoes. The released DPPa may conjugate with overexpressed BSA-SOH, which results in the recovery of fluorescence signal, which can be used as indicator for CL release, and photodynamic effect. More importantly, such conjugation transfers DPPa from a small molecule PS into a macromolecular PS with long tumor retention time and treatment window of PDT, which enables multiple PDT. This study thus provides an effective strategy to prolong the treatment window of PDT and enables tumor-specific fluorescence imaging-guided combination therapy. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.