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.