Prolonging Treatment Window of Photodynamic Therapy with Self-Amplified H2O2-Activated Photodynamic/Chemo Combination Therapeutic Nanomedicines

Photodynamic therapy (PDT) is a promising approach to 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 a single injection. In this study, a tumor-specific phototheranostic nanomedicine (DPPa NP) is developed for photodynamic/chemo combination therapy with a prolonged PDT treatment window. DPPa NP is prepared via encapsulating a hydrophobic oxidized bovine serum albumin (BSA-SOH)-conjugatable PS DPPa with amphiphilic H2O2-activatable chlorambucil (CL) prodrug mPEG-TK-CL. The released CL under H2O2 treatment can not only kill tumor cells but also upregulate reactive oxygen species levels within tumor cells, leading to the almost full release of cargoes. The released DPPa may conjugate with overexpressed BSA-SOH, which results in the recovery of the fluorescence signal and photodynamic effect. More importantly, such conjugation transfers DPPa from a small molecule PS into a macromolecular PS with a 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.