Endoplasmic Reticulum-Targeted Aggregation-Induced Emission Luminogen for Synergetic Tumor Ablation with Glibenclamide

Yifan Wu; Xiaohui Chen; Liwei Zhu; Deliang Wang; Xue Li; Jiayi Song; Dong Wang; Xiyong Yu; Ying Li; Ben Zhong Tang

doi:10.1021/acsami.3c10940

Endoplasmic Reticulum-Targeted Aggregation-Induced Emission Luminogen for Synergetic Tumor Ablation with Glibenclamide

ACS Appl Mater Interfaces. 2023 Oct 30. doi: 10.1021/acsami.3c10940. Online ahead of print.

Authors

Yifan Wu^{1

2}, Xiaohui Chen^{1

3}, Liwei Zhu⁴, Deliang Wang⁵, Xue Li^{1

2}, Jiayi Song⁴, Dong Wang¹, Xiyong Yu⁴, Ying Li^{1

4}, Ben Zhong Tang⁶

Affiliations

¹ Center for AIE Research, Shenzhen Key Laboratory of Polymer Science and Technology, Guangdong Research Center for Interfacial Engineering of Functional Materials, College of Materials Science and Engineering, Shenzhen University, Shenzhen, Guangdong 518060, China.
² Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen, Guangdong 518060, China.
³ Institute of Laboratory Medicine, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, School of Medical Technology, Guangdong Medical University, Dongguan, Guangdong 523808, China.
⁴ Innovation Research Center for AIE Pharmaceutical Biology, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 511436, China.
⁵ Department of Materials Chemistry, Huzhou University, Huzhou, Zhejiang 313000, China.
⁶ Shenzhen Institute of Aggregate Science and Engineering, School of Science and Engineering, The Chinese University of Hong Kong, Shenzhen, Guangdong 518172, China.

PMID: 37903083
DOI: 10.1021/acsami.3c10940

Abstract

Photodynamic therapy based on fluorescence illumination of subcellular organelles and in situ bursts of reactive oxygen species (ROS) has been recognized as a promising strategy for cancer theranostics. However, the short life of ROS and unclarified anticancer mechanism seriously restrict the application. Herein, we rationally designed and facilely synthesized a 2,6-dimethylpyridine-based triphenylamine (TPA) derivative TPA-DMPy with aggregation-induced emission (AIE) features and production of type-I ROS. Except for its selective binding to the endoplasmic reticulum (ER), TPA-DMPy, in synergy with glibenclamide, a medicinal agent used against diabetes, induced significant apoptosis of cancer cells in vitro and in vivo. Additionally, TPA-DMPy greatly incited the release of calcium from ER upon light irradiation to further aggravate the depolarization of ER membrane potential caused by glibenclamide, thus inducing fatal ER stress and crosstalk between ER and mitochondria. Our study extends the biological design and application of AIE luminogens and provides new insights into discovering novel anticancer targets and agents.

Keywords: ATP-sensitive potassium channels; aggregation-induced emission; calcium; cancer theranostics; endoplasmic reticulum stress.