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

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.

• Authors: Shuai Guo, Liang Qiu, Yafei Chen, Xuzhao Wang, Biao Ma, Chang Qu, Jianmin Cui, Hailin Zhang, Chengfen Xing, Yong Zhan, Hailong An
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 178 Pg. 114062 (08 2020) ISSN: 1873-2968 [Electronic] England
• PMID: 32492446 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

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

Topics

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