Biodegradable Quantum Composites for Synergistic Photothermal Therapy and Copper-Enhanced Chemotherapy

ACS Appl Mater Interfaces. 2020 Oct 21;12(42):47289-47298. doi: 10.1021/acsami.0c14636. Epub 2020 Oct 7.

Abstract

In recent times, the combination therapy has garnered enormous interest owing to its great potential in clinical research. It has been reported that disulfiram, a clinical antialcoholism drug, could be degraded to diethyldithiocarbamate (DDTC) in vivo and subsequently result in the copper-DDTC complex (Cu(DDTC)2) toward ablating cancer cells. In addition, the ultrasmall copper sulfide nanodots (CuS NDs) have shown great potential in cancer treatment because of their excellent photothermal and photodynamic therapeutic efficiencies. Herein, by taking advantage of the interactions between CuS and DDTC, a new multifunctional nanoplatform based on DDTC-loaded CuS (CuS-DDTC) NDs is successfully fabricated, leading to the achievement of the synergistic effect of photothermal and copper enhanced chemotherapy. All experimental results verified promising synergistic therapeutic effects. Moreover, in vivo biocompatibility and metabolism experiments displayed that the CuS-DDTC NDs could be quickly excreted from the body with no apparent toxicity signs. Together, our findings indicated the superior synergistic therapeutic effect of photothermal and copper-enhanced chemotherapy, providing a promising anticancer strategy based on the CuS-DDTC NDs drug delivery system.

Keywords: disulfiram; ion-enhanced chemotherapy; photothermal; synergistic effect; ultrasmall copper sulfides nanodots.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Coordination Complexes / chemical synthesis
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology*
  • Copper / chemistry
  • Copper / pharmacology*
  • Ditiocarb / chemistry
  • Ditiocarb / pharmacology*
  • Drug Screening Assays, Antitumor
  • Female
  • Mammary Neoplasms, Experimental / drug therapy
  • Mammary Neoplasms, Experimental / metabolism
  • Mammary Neoplasms, Experimental / pathology
  • Mice
  • Mice, Inbred Strains
  • Nanoparticles / chemistry
  • Particle Size
  • Photothermal Therapy*
  • Sulfides / chemistry
  • Sulfides / pharmacology*
  • Surface Properties

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • Sulfides
  • Copper
  • Ditiocarb