Utilizing dual-responsive iridium(Ⅲ) complex for hepatocellular carcinoma: Integrating photoacoustic imaging with chemotherapy and photodynamic therapy

Stimuli-triggered release and alleviating resistance of iridium(III)-based drugs at tumor sites remains challengeable for clinical hepatoma therapy. Herein, a doxorubicin@iridium-transferrin(DOX@IrTF) nanovesicle was synthesized by carboxylated-transferrin(TF) and doxorubicin-loaded amphiphilic iridium-amino with quaternary ammonium(QA) groups and disulfide bonds. The QA groups enhanced photophysical properties and broadened production capacity of photoinduced-reactive oxygen species(ROS), while the disulfide-bridged bonds regulated oxidative stress levels through reacting with glutathione(GSH); simultaneously, modification of TF improved recognition and endocytosis of the nanovesicle for tumor cells. Based on in-vitro results, a controlled-release behavior of DOX upon a dualresponsiveness of GSH and near-infrared ray(NIR) irradiation was presented, along with high-efficiency generation of ROS. After an intravenous injection, the nanovesicle was targeted at tumor sites, realizing TF-navigated photoacoustic imaging guidance and synergistic chemotherapy-photodynamic therapy under NIR/GSH stimulations. Overall, newly-synthesized DOX@Ir-TF nanovesicle provided a potential in subcutaneous hepatocellular carcinoma therapy due to integrations of targeting delivery, dual-stimuli responsive release, synergistic therapy strategy, and real-time monitoring.