Targeting protein degradation is recognized as a valid approach to cancer therapy. The ubiquitin–proteasome system (UPS) and the autophagy–lysosome pathway are two major pathways for intracellular protein degradation. Proteasome inhibitors such as bortezomib are clinically approved for treating malignancies, but to date, they are still unsatisfactory for cancer therapy. This study identifies titania‐coated gold nano‐bipyramid (NBP/TiO2) nanostructures as an autophagic flux inhibitor, as the smallest NBP/TiO2 nanostructures induce significant autophagosome accumulation in human glioblastoma U‐87 MG cells via blocking the autophagosome–lysosome fusion process and inhibiting lysosomal degradation. Further study indicates that NBP/TiO2 nanostructures reduce the intracellular level of mature cathepsin B and directly inhibit the proteolytic activity of cathepsin B, thereby further inhibiting trypsin‐like proteolytic activity, which is a potential cotarget for UPS inhibition. NBP/TiO2 nanostructures interact synergistically with bortezomib to suppress the viability of U‐87 MG cells, as the combined treatment synergistically induces the intracellular accumulation of ubiquitinated protein and endoplasmic reticulum stress. In addition, photothermal therapy further synergistically reduces the cell viability. In summary, this study suggests that NBP/TiO2 nanostructures function as a promising anticancer agent in combination with proteasome inhibitors.
Photothermal agents with strong light absorption in the second near-infrared (NIR-II) region (1000–1350 nm) are strongly desired for successful photothermal therapy (PTT). In this work, titania-coated Au nanobipyramids (NBP@TiO2) with a strong plasmon resonance in the NIR-II window were synthesized. The NBP@TiO2 nanostructures have a high photothermal conversion efficiency of (93.3 ± 5.2)% under 1064-nm laser irradiation. They are also capable for loading an anticancer drug combretastatin A-4 phosphate (CA4P). In vitro PTT studies reveal that 1064-nm laser irradiation can efficiently ablate human lung cancer A549 cells and enhance the anticancer effect of CA4P. Moreover, the CA4P-loaded NBP@TiO2 nanostructures combined with PTT induce a synergistic antiangiogenesis effect. In vivo studies show that such CA4P-loaded NBP@TiO2 nanostructures under mild 1064-nm laser irradiation at an optical power density of 0.4 W cm−2, which is lower than the skin tolerance threshold value, exhibit a superior antitumor effect. This work presents not only the development of the NBP@TiO2 nanostructures as a novel photothermal agent responsive in the NIR-II window but also a unique combined chemo-photothermal therapy strategy for cancer therapy.
20 November 2023 in ACS Applied Materials & Interfaces
Transferring traditional plasmonic noble metal nanomaterials from the laboratory to industrial production has remained challenging due to the high price of noble metals. The development of cost-effective non-noble-metal alternatives with outstanding plasmonic properties has therefore become essential. Herein, we report on the gram-scale production of differently shaped TiN nanoparticles with strong plasmon-enabled broadband light absorption, including differently sized TiN nanospheres, nanobipyramids, and nanorod arrays. The TiN nanospheres and nanobipyramids are further coembedded in highly porous poly(vinyl alcohol) films to function as a photothermal material for solar seawater desalination. A seawater evaporation rate of 3.8 kg m-2 h-1 is achieved, which marks the record performance among all plasmonic solar seawater desalination systems reported so far. The removal percentage of phenol reaches 98.3%, which is attributed to the joint action of the excellent photocatalytic ability and the superhydrophilicity of the porous TiN-based composite film.