Triple-helix β-glucan-based self-assemblies, synthesis, characterization and anticarcinogenic effect.

Abstract

Triple negative breast cancer (TNBC) seriously endangers women's life and health due to its high invasion and mortality. Reactive oxygen species (ROS) mediated tumor cells apoptosis is considered an effective anticancer approach. Herein, we designed a natural active triple helix β-Glucan (BFP) wrapped single walled carbon nanotubes (SWNTs)-loaded doxorubicin (DOX) self-assembly (BSD) via generating excess ROS to induce oxidative stress damage for TNBC therapy. BSD could directly consume glutathione (GSH) to promote ROS. In vitro results demonstrated that BSD exhibited obvious antitumor effects to breast cancer cells by promoting apoptosis. Un-targeted metabolomics under molecular level identified the specific metabolic targets and unveiled that BSD markedly disturbed multiple metabolic pathways, including purine metabolism, pentose phosphate pathway, glutathione metabolism pathways, amino sugar and nucleotide sugar metabolism and energy metabolism, led to the inhibition of DNA and RNA synthesis, the generation of ROS, the exacerbation of DNA damage, the disruption of cell membrane integrity and the decrease of ATP. In vitro and in vivo oxidative stress assays further verified that BSD significantly promoted intracellular oxidative stress and resulted in cell damage. This study provides theoretical basis for the development and screening of new drugs based on ROS therapy for TNBC.