Prolonging Treatment Window of Photodynamic Therapy with Self-Amplified H 2 O 2 -Activated Photodynamic/Chemo Combination Therapeutic Nanomedicines.

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 H 2 O 2 -activatable chlorambucil (CL) prodrug mPEG-TK-CL. Such a design enables simultaneous release of CL and DPPa under the treatment of H 2 O 2 . 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.