An ROS-sensitive tegafur-PpIX-heterodimer-loaded in situ injectable thermosensitive hydrogel for photodynamic therapy combined with chemotherapy to enhance the tegafur-based treatment of breast cancer

Abstract

Chemotherapy and surgery are commonly used clinical treatments for breast cancer. However, unsatisfactory therapeutic effects, unavoidable side effects, and the removal of breast tissue during surgery are still major obstacles to be overcome during breast-cancer treatment. To overcome the aforementioned issues, a biomimetic and thermosensitive hydrogel encapsulating reactive oxygen species (ROS)-sensitive tegafur (TF)-protoporphyrin IX (PpIX) heterodimers (TTP) was prepared aimed at the strategy of synergizing chemotherapy and photodynamic therapy. TF was grafted onto the photosensitizer PpIX through ROS-sensitive thioether bonds. Under 630 nm laser irradiation, the ROS concentration in tumors was increased to help drug release. The “on-demand” drug release maximized the therapeutic effects of TF and effectively reduced its toxicity. Particularly, the ROS concentration was increased, and it was expected that the tumor-cell-killing abilities of ROS could be exploited. A hydrogel formed from temperature-sensitive chitosan and silk sericin was selected as a drug carrier, which formed a drug reservoir intratumorally after intratumoral injection. Intratumoral injection gave the drug precise and long-term release behavior, which allowed for the clever avoidance of various physical and biological barriers in vivo. In vivo and in vitro studies prove that the use of this TTP hydrogel provides a new attempt to overcome the many difficulties related to breast-cancer treatment simultaneously, and this study opens up new paths for breast-cancer treatment.