Albumin-assembled copper-bismuth bimetallic sulfide bioactive nanosphere as an amplifier of oxidative stress for enhanced radio-chemodynamic combination therapy

Abstract

The tumor microenvironment with overexpressed hydrogen peroxide (H2O2) and reinforced antioxidative system (glutathione, GSH) becomes a double-edged sword for the accessibility of nano-therapy. Since reactive oxygen species (ROS) are easily quenched by the developed antioxidative network, ROS based treatments such as chemodynamic therapy (CDT) and radiotherapy (RT) for killing cancer cells are severely attenuated. To overcome such limitations, a bioactive nanosphere system is developed to regulate intracellular oxidative stress for enhanced radio-chemodynamic combination therapy by using bovine serum albumin (BSA) based bioactive nanospheres that are BSA assembled with in situ generated copper-bismuth sulfide nanodots and diallyl trisulfide (DATS). The copper-bismuth sulfide nanodots react with H2O2 to produce •OH and release Cu2+. Then, the Cu2+ further depletes GSH to generate Cu+ for more •OH generation in the way of Fenton-like reaction. Such a cascade reaction can initiate •OH generation and GSH consumption to realize chemodynamic therapy. The elevation of ROS triggered by the DATS from BBCD nanospheres further augments the breaking of redox balance for the increased oxidative stress in 4T1 cells. With the sensitization of increased oxidative stress and high Z element Bi, an enhanced radio-chemodynamic combination therapy is achieved. The current work provides an enhanced radio-chemodynamic combination treatment for the majority of solid tumors by using the co-assembled bioactive nanospheres as an amplifier of oxidative stress.

In Situ Formed Z-Scheme Graphdiyne Heterojunction Realizes NIR-Photocatalytic Oxygen Evolution and Selective Radiosensitization for Hypoxic Tumors

“…The 4T1 cells of CuO@GDY + X-ray group had the strongest positive DCF signals, indicating that X-ray-activated CuO@GDY nanocatalyst enabled to accelerate ·OH generation inside tumor cells. In contrast, no significant difference of the DCF signal on HUVECs with the same treatments was observed, which reflected that the Fenton-like behavior was prevented inside normal cells with deficient H 2 O 2 expression. , The tumor-specific highly toxic ·OH burst can be accelerated by exogenous stimulus X-rays, enhancing the controllability of catalytic therapy compared to other spontaneous therapy nanoplatforms based on catalytic or enzyme-mimic activities, − which indicated the potential of CuO@GDY-mediated selective radiosensitization. To further determine whether X-ray-activated CuO@GDY could selectively kill tumor cells, the intuitive cell death assay was then performed.…”