Oxygen-Deficient BiOCl Combined with L-Buthionine-Sulfoximine Synergistically Suppresses Tumor Growth through Enhanced Singlet Oxygen Generation under Ultrasound Irradiation

Small. 2022 Mar;18(9):e2104550. doi: 10.1002/smll.202104550. Epub 2021 Dec 15.

Abstract

Excess generation of reactive oxygen species (ROS) based on sensitizers under ultrasound (US) excitation can cause the death of tumor cells via oxidative damage, but sonosensitizers are largely unexplored. Herein, oxygen-deficient black BiOCl (B-BiOCl) nanoplates (NPs) are reported, with post-treatment on conventional BiOCl by simple UV excitation, showing stronger singlet oxygen (1 O2 ) generation than commercial TiO2 nanoparticles and their derivatives under US irradiation. Moreover, L-buthionine-sulfoximine (BSO), a GSH biosynthesis inhibitor, is incorporated into B-BiOCl NPs. The authors find that BSO can be released owing to the degradation of B-BiOCl NPs in the presence of acid and GSH, which are overexpressed in tumors. The results show that BSO/B-BiOCl-PEG NPs have a multifunctional synergistic effect on improving ROS production. In particular, BiOCl has remarkable near-infrared light absorption after UV treatment and is good for photoacoustic imaging that can guide subsequent sonodynamic therapy. This work shows that just with a simple oxygen deficiency treatment, strong 1 O2 generation can be provided to a conventional material under US irradiation and, interestingly, this effect can be amplified by using a small inhibitor BSO, and this is clearly demonstrated in cell and mice experiments.

Keywords: BiOCl; GSH inhibitors; defect engineering; oxidative stress; reactive oxygen species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Glutathione* / metabolism
  • Hypoxia
  • Methionine / analogs & derivatives
  • Mice
  • Oxygen
  • Reactive Oxygen Species / metabolism
  • Singlet Oxygen*

Substances

  • Reactive Oxygen Species
  • Singlet Oxygen
  • buthionine
  • Methionine
  • Glutathione
  • Oxygen