Open AccessTitania‐Coated Gold Nano‐Bipyramids for Blocking Autophagy Flux and Sensitizing Cancer Cells to Proteasome Inhibitor‐Induced Death
Author(s) -
Wan HongYe,
Chen JianLi,
Zhu Xingzhong,
Liu Liang,
Wang Jianfang,
Zhu XiaoMing
Publication year - 2018
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.201700585
Subject(s) - autophagy , autophagosome , lysosome , bortezomib , cathepsin b , proteasome inhibitor , cancer cell , microbiology and biotechnology , proteasome , intracellular , protein degradation , viability assay , endoplasmic reticulum , cathepsin , chemistry , biochemistry , cell , biology , cancer , apoptosis , enzyme , immunology , multiple myeloma , genetics
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/TiO 2 ) nanostructures as an autophagic flux inhibitor, as the smallest NBP/TiO 2 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/TiO 2 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/TiO 2 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/TiO 2 nanostructures function as a promising anticancer agent in combination with proteasome inhibitors.