Enhancing Hepatocellular Carcinoma Therapy with DOX-Loaded SiO2 Nanoparticles via mTOR-TFEB Pathway Autophagic Flux Inhibition
Author:
Chen Huanyu1, Liu Jun2, Cao Zhichao1, Li Jiajia3, Zhang Hong1, Yang Qianqian1, Shen Yuxian2, He Kewu1
Affiliation:
1. the Third Affiliated Hospital of Anhui Medical University 2. Anhui Medical University 3. The First Affiliated Hospital of Anhui Medical University
Abstract
Abstract
Chemotherapeutic drugs often fail to provide long-term efficacy due to their lack of specificity and high toxicity. To enhance the biosafety and reduce the side effects of these drugs, various nanocarrier delivery systems have been developed. In this study, we loaded the anticancer drug doxorubicin (DOX) and an MRI contrast agent into silica nanoparticles, coating them with pH-responsive and tumor cell-targeting polymers. These polymers enable the carrier to achieve targeted delivery and controlled drug release in acidic environments. This integrated diagnostic and therapeutic strategy successfully achieved both the diagnosis and treatment of liver cancer. Additionally, we demonstrated that the nanocarrier inhibits autophagic flux in liver cancer cells by targeting the autophagy-lysosome pathway and regulating the nuclear translocation of TFEB, thereby promoting tumor cell death. This novel diagnostic-integrated nanocarrier is expected to be a promising tool for targeted liver cancer treatment.
Publisher
Springer Science and Business Media LLC
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