Near-infrared-triggered in situ hybrid hydrogel system for synergistic cancer therapy

Abstract

As one of the most frequently used chemotherapeutic drugs, doxorubicin (DOX) is accompanied by low accumulation in tumors and severe dose-limiting side effects with systemic administration, which limits its therapeutic index. In this work, a novel and injectable in situ photo-sensitive inorganic/organic hybrid hydrogel as a localized drug-delivery system was examined. It explored poly(ethylene glycol) double acrylates (PEGDA) as a polymeric matrix, DOX as a model drug, a TiO₂@MWCNT nanocomposite as the photoinitiator and photosensitizer–photothermal agent for tumor therapy possessing a multi-mechanism using a single NIR laser. Briefly, a PEGDA solution containing DOX and TiO₂@MWCNTs was injected into a tumor and rapidly gelled in vivo via a photo-crosslinking action triggered by a NIR laser. DOX release from the DOX/TiO₂@MWCNTs/PEGDA hydrogel was sustained and long-lasting, over 10 days, indicating that the PEGDA gel acted as a drug depot. Simultaneously, a NIR laser light was adopted which can be absorbed and converted into reactive oxygen species (ROS) or local hyperthermia by TiO₂@MWCNTs, leading to tumor cell death. This DOX/TiO₂@MWCNTs/PEGDA hydrogel exhibited remarkable anti-proliferative activities against MCF-7 cancer cells in vitro. Experiments in vivo showed that a single intratumoral injection of this hydrogel with 808 nm laser irradiation was the most effective among all DOX formulations in the tumor-bearing mice models. There was a relatively small DOX distribution in normal tissues and much lower systemic toxicity than the control group (DOX-only). In general, it is believed that the novel photo-sensitive hybrid hydrogel system prepared in this study can afford high drug-loading, sustained and stable drug release, as well as repeated phototherapy of the tumor with the administration of a single dose.