Abstract
Stimuli-triggered release and alleviating resistance of iridium(Ⅲ)-based drugs at tumor sites re-mains challengeable for clinical hepatoma therapy.Herein,a doxorubicin@iridium-transferrin(DOX@Ir-TF)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 glu-tathione(GSH);simultaneously,modification of TF improved recognition and endocytosis of the nanovesi-cle for tumor cells.Based on in-vitro results,a controlled-release behavior of DOX upon a dual-responsiveness 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 subcuta-neous hepatocellular carcinoma therapy due to integrations of targeting delivery,dual-stimuli responsive release,synergistic therapy strategy,and real-time monitoring.
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