TMEM16A-inhibitor loaded pH-responsive nanoparticles: A novel dual-targeting antitumor therapy for lung adenocarcinoma

Biochem Pharmacol. 2020 Aug:178:114062. doi: 10.1016/j.bcp.2020.114062. Epub 2020 May 31.

Abstract

To overcome the adverse effects of conventional chemotherapy for cancers, various nanoparticles based drug delivery systems have been developed. However, nanoparticles delivering drugs directly to kill tumor cells still faced with challenges, because tumors possessed adopt complex mechanism to resist damages, which compromised the therapeutic efficacy. TMEM16A/CaCCs (Calcium activates chloride channels) has been identified to be overexpressed in lung adenocarcinoma which can serve as a novel tumor specific drug target in our previous work. Here, we developed a novel dual-targeted antitumor strategy via designing a novel nano-assembled, pH-sensitive drug-delivery system loading with specific inhibitors of TMEM16A against lung adenocarcinoma. For validation, we assayed the novel dual-targeting therapy on xenograft mouse model which exhibited significant antitumor activity and not affect mouse body weight. The dual targeting therapy accomplished in this study will shed light on the development of advanced antitumor strategy.

Keywords: Dual-targeting antitumor strategy; Ion channel; Lung adenocarcinoma; TMEM16A; pH-responsive nanocarriers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung / drug therapy
  • Adenocarcinoma of Lung / metabolism*
  • Animals
  • Anoctamin-1 / antagonists & inhibitors*
  • Anoctamin-1 / metabolism*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Dose-Response Relationship, Drug
  • Drug Delivery Systems / methods*
  • HEK293 Cells
  • Humans
  • Hydrogen-Ion Concentration
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism*
  • Mice
  • Mice, Nude
  • Nanoparticles / administration & dosage*
  • Neoplasm Proteins / antagonists & inhibitors*
  • Neoplasm Proteins / metabolism*

Substances

  • ANO1 protein, human
  • Anoctamin-1
  • Neoplasm Proteins