Frontiers in Immunology (Dec 2022)

Graphene quantum dots induce cascadic apoptosis via interaction with proteins associated with anti-oxidation after endocytosis by Trypanosoma brucei

  • Yiwei Xie,
  • Yiwei Xie,
  • Yiwei Xie,
  • Hongrui Liang,
  • Hongrui Liang,
  • Hongrui Liang,
  • Ning Jiang,
  • Ning Jiang,
  • Ning Jiang,
  • Dingyuan Liu,
  • Dingyuan Liu,
  • Dingyuan Liu,
  • Naiwen Zhang,
  • Naiwen Zhang,
  • Naiwen Zhang,
  • Qilong Li,
  • Qilong Li,
  • Qilong Li,
  • Kai Zhang,
  • Kai Zhang,
  • Kai Zhang,
  • Xiaoyu Sang,
  • Xiaoyu Sang,
  • Xiaoyu Sang,
  • Ying Feng,
  • Ying Feng,
  • Ying Feng,
  • Ran Chen,
  • Ran Chen,
  • Ran Chen,
  • Yiwei Zhang,
  • Yiwei Zhang,
  • Yiwei Zhang,
  • Qijun Chen,
  • Qijun Chen,
  • Qijun Chen

DOI
https://doi.org/10.3389/fimmu.2022.1022050
Journal volume & issue
Vol. 13

Abstract

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Trypanosoma brucei, the pathogen causing African sleeping sickness (trypanosomiasis) in humans, causes debilitating diseases in many regions of the world, but mainly in African countries with tropical and subtropical climates. Enormous efforts have been devoted to controlling trypanosomiasis, including expanding vector control programs, searching for novel anti-trypanosomial agents, and developing vaccines, but with limited success. In this study, we systematically investigated the effect of graphene quantum dots (GQDs) on trypanosomal parasites and their underlying mechanisms. Ultrasmall-sized GQDs can be efficiently endocytosed by T. brucei and with no toxicity to mammalian-derived cells, triggering a cascade of apoptotic reactions, including mitochondrial disorder, intracellular reactive oxygen species (ROS) elevation, Ca2+ accumulation, DNA fragmentation, adenosine triphosphate (ATP) synthesis impairment, and cell cycle arrest. All of these were caused by the direct interaction between GQDs and the proteins associated with cell apoptosis and anti-oxidation responses, such as trypanothione reductase (TryR), a key protein in anti-oxidation. GQDs specifically inhibited the enzymatic activity of TryR, leading to a reduction in the antioxidant capacity and, ultimately, parasite apoptotic death. These data, for the first time, provide a basis for the exploration of GQDs in the development of anti-trypanosomials.

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