Copper phosphate-rotenone nanocomposites for tumor therapy through autophagy blockage-enhanced triphosadenine supply interruption and lipid peroxidation accumulation.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
  • Additional Information
    • Abstract:
      • The biodegradable copper phosphate-rotenone nanocomposites were constructed. • These nanocomposites caused mitochondria dysfunction to cut off energy supply. • Intracellular autophagy process was disrupted to inactivate the self-repairing capacity. • Tumor elimination was achieved through enhanced damage accumulation. Malignant tumor cells feature rapid metabolism and proliferation that need a large amount of energy to maintain these physiological activities. Blocking energy supply through mitochondria dysfunction is an alternative strategy but is hindered by the limited blockage efficacy and the repairation of cytoprotective autophagy. Herein, a novel kind of bull serum albumin (BSA)-coated rotenone (RO)-copper phosphate (CuPi) nanocompsites was prepared for tumor therapy through autophagy blockage-enhanced triphosadenine (ATP) supply interruption and lipid peroxidation (LPO) accumulation. When internalization by tumor cells, these formed BSA-RO-CuPi nanoparticles (NPs) degraded to release RO, Cu2+, and PO 4 3−. RO acts on mitochondrial complex I and reduces the activity of Fe-S clusters, and Cu2+ is reduced into Cu+ by ferredoxin 1 (FDX1) to induce dihydrolipoamide S-acetyltransferase (DLAT) aggregation. Thus, mitochondria function is severely damaged to cut off ATP supply. Meanwhile, Cu2+ depletes glutathione (GSH) through a redox reaction and produces hydroxyl radicals through the Fenton-like reaction, inducing the generation of LPO. Importantly, PO 4 3− weakens lysosomal acidity to disrupt the autophagy capacity of tumor cells, resulting in damage accumulation. In vivo data demonstrated that these developed BSA-RO-CuPi NPs show desirable antitumor capacity and emphasize the importance of mitochondria dysfunction in tumor treatment applications. [ABSTRACT FROM AUTHOR]
    • Abstract:
      Copyright of Chemical Engineering Journal is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)