A silica nanobean carrier utilizing lysosomal and mitochondrial autophagy to kill ovarian cancer cell
Shi Tang,
Qing Liu,
Mingcheng Song,
Xiangshuai Li,
Degang Ji,
Ying-Wei Yang,
Huimei Yu
Affiliations
Shi Tang
Key Laboratory of Pathobiology, Ministry of Education, Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China
Qing Liu
Key Laboratory of Pathobiology, Ministry of Education, Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China
Mingcheng Song
Key Laboratory of Pathobiology, Ministry of Education, Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China
Xiangshuai Li
College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012, China
Degang Ji
China-Japan Union Hospital of Jilin University, Jilin University, Changchun 130031, China
Ying-Wei Yang
College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012, China
Huimei Yu
Key Laboratory of Pathobiology, Ministry of Education, Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China
The development of responsive and smart drug nanocarriers that defeat the tumor microenvironment that resists cancer therapy has attracted considerable attention in recent decades. Upgrades are sought to effectively increase the therapeutic efficacy of chemotherapy drugs and reduce damage to normal tissues. In this study, a new type of silica nano-particle carrier, dual-functionalized mesoporous silica nanobeans (DF-MSNB), is used to encapsulate the drug, doxorubicin (DOX), to form the DOX@DF-MSNB complex. The complex simultaneously releases drugs and tracks drug uptake by cells after the environmentally triggered release of the encapsulated drug and fluorophore. Upon sensing the high GSH level and low pH in the tumor microenvironment, the disulfide bond breaks in the linker between the drug and the carrier. An attached fluorescent group is activated, and the DOX drug is released from the carrier. Our results show that DOX@DF-MSNB co-localizes with mitochondria and lysosomes in A2780 cells, enabling DOX to subvert the cells’ mitochondrial function and activate macrophage and mitochondrial autophagy. The application of a mitochondrial autophagy inhibitor confirms that DOX@DF-MSNB inhibits tumor development by activating mitochondrial autophagy.
