Arsenene Nanodots with Selective Killing Effects and their Low-Dose Combination with ß-Elemene for Cancer Therapy

Adv Mater. 2021 Sep;33(37):e2102054. doi: 10.1002/adma.202102054. Epub 2021 Jul 26.

Abstract

Arsenical drugs have achieved hallmark success in treating patients with acute promyelocytic leukemia, but expanding their clinical utility to solid tumors has proven difficult with the contradiction between the therapeutic efficacy and the systemic toxicity. Here, leveraging efforts from materials science, biocompatible PEGylated arsenene nanodots (AsNDs@PEG) with high monoelemental arsenic purity that can selectively and effectively treat solid tumors are synthesized. The intrinsic selective killing effect of AsNDs@PEG is closely related to high oxidative stress in tumor cells, which leads to an activated valence-change of arsenic (from less toxic As0 to severely toxic oxidation states), followed by decreased superoxide dismutase activity and massive reactive oxygen species (ROS) production. These effects occur selectively within cancer cells, causing mitochondrial damage, cell-cycle arrest, and DNA damage. Moreover, AsNDs@PEG when applied in a multi-drug combination strategy with β-elemene, a plant-derived anticancer drug, achieves synergistic antitumor outcomes, and its newly discovered on-demand photothermal properties facilitate the elimination of the tumors without recurrence, potentially further expanding its clinical utility. In line of the practicability for a large-scale fabrication and negligible systemic toxicity of AsNDs@PEG (even at high doses and with repetitive administration), a new-concept arsenical drug with high therapeutic efficacy for selective solid tumor therapy is provided.

Keywords: 2D materials; arsenene nanodots; combination cancer therapy; selective killing effects; ß-elemene.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Arsenic / chemistry*
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • DNA Damage / drug effects
  • Drug Therapy, Combination
  • Humans
  • Infrared Rays
  • Mice
  • Mice, Nude
  • Nanoparticles / chemistry*
  • Nanoparticles / therapeutic use
  • Nanoparticles / toxicity
  • Neoplasms / drug therapy
  • Neoplasms / pathology
  • Oxidative Stress / drug effects
  • Photothermal Therapy
  • Polyethylene Glycols / chemistry
  • Reactive Oxygen Species / metabolism
  • Sesquiterpenes / chemistry
  • Sesquiterpenes / pharmacology*
  • Sesquiterpenes / therapeutic use
  • Transplantation, Heterologous

Substances

  • Antineoplastic Agents
  • Reactive Oxygen Species
  • Sesquiterpenes
  • beta-elemene
  • Polyethylene Glycols
  • Arsenic