Effect of ROS generation on highly dispersed 4-layer O-Ti7O13 nanosheets toward tumor synergistic therapy.

Ultra-thin two-dimensional nanosheets have attracted increasing attention due to their great application prospects in nanomaterial science and biomedicine. Herein, we report the preparation of exfoliated raw and oxidized 4-layer Ti7O13 (O-Ti7O13) and their ability to produce reactive oxygen species (ROS). The results show that O-Ti7O13 nanosheets can effectively produce ROS induced by X-ray irradiation. The 4-layer nanosheets can quickly load doxorubicin (DOX) within 5 min with a high loading rate to obtain a novel nanodrug system through their electrostatic adsorption capacity, and they exhibit a sustained release behavior. In this way, chemotherapy, radiation therapy and photodynamic therapy effectively combine for cancer synergistic treatment. We evaluated the cytotoxicity, cellular uptake and intracellular location of the O-Ti7O13 nanosheet-based drug delivery system in A549 lung cancer cells. Our results show that the O-Ti7O13/DOX complex is more cytotoxic to A549 cells than free DOX since a low concentration of loaded DOX (10 µg/mL) with a low dose of X-rays can cause the complete apoptosis of tumor cells. This work reveals that the therapeutic effect of DOX-loaded O-Ti7O13 nanosheets is strongly dependent on their loading mode, and the effects of chemotherapy and photodynamic therapy are enhanced under X-ray irradiation, which allows O-Ti7O13 nanosheet use as a photo-activated drug carrier. This work provides a new strategy for preparing 2D metal oxide nanosheets toward biomedical applications.

SiO2-coated magnetic nano-Fe3O4 photosensitizer for synergistic tumour-targeted chemo-photothermal therapy.

In this study, we integrated chemotherapy and photothermal therapy in a magnetically targeted doxorubicin-loaded Fe3O4@SiO2 nanodrug system. Size-controllable magnetic Fe3O4@SiO2 core-shell nanoparticles were synthesized via a solvothermal method and a modified Stǒber method. A molecular anticancer drug, namely, doxorubicin, was loaded onto Fe3O4@SiO2 nanocomposites to form a magnetically targeted drug delivery system. This drug delivery system exhibits pH-sensitive effects on drug loading and release. The drug loading rate in a neutral environment is higher than that in an acidic environment; the opposite property is observed for the release rate. In addition, the magnetic Fe3O4@SiO2 nanocomposites exhibit a satisfactory photothermal effect under NIR (808 nm) irradiation. The temperature can increase to 55 °C after only 10 min of irradiation, which effectively induces apoptosis of cancer cells in vitro. The cytotoxicity and cellular uptake of Fe3O4@SiO2@DOX nanodrugs were evaluated in A549 lung cancer cells. After treatment with Fe3O4@SiO2@DOX that contains only 10 µg/mL of DOX, 82.8% of A549 lung cancer cells can be killed. Furthermore, 81.3% of A549 lung cancer cells are killed after incubation with Fe3O4@SiO2@DOX that contains only 0.5 µg/mL of DOX and 15 min of NIR irradiation, thereby suggesting an excellent synergistic chemo-photothermal effect in tumour therapy. Our results suggest a new approach for the synthesis of a multifunctional, highly targeted, size-controlled nanodrug for tumour synergistic therapy.