Enhancing hepatocellular carcinoma therapy with DOX-loaded SiO2 nanoparticles via mTOR-TFEB pathway autophagic flux inhibition
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 dox...
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| Format: | Article |
| Language: | English |
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BMC
2025-01-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03107-5 |
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| author | Huanyu Chen Jun Liu Zhichao Cao Jiajia Li Hong Zhang Qianqian Yang Jian Cheng Yuxian Shen Kewu He |
| author_facet | Huanyu Chen Jun Liu Zhichao Cao Jiajia Li Hong Zhang Qianqian Yang Jian Cheng Yuxian Shen Kewu He |
| author_sort | Huanyu Chen |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-795a9eb5481f4677b62dc85b585856e2 |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-795a9eb5481f4677b62dc85b585856e22025-01-19T12:37:52ZengBMCJournal of Nanobiotechnology1477-31552025-01-0123111610.1186/s12951-025-03107-5Enhancing hepatocellular carcinoma therapy with DOX-loaded SiO2 nanoparticles via mTOR-TFEB pathway autophagic flux inhibitionHuanyu Chen0Jun Liu1Zhichao Cao2Jiajia Li3Hong Zhang4Qianqian Yang5Jian Cheng6Yuxian Shen7Kewu He8Imaging Center, The Third Affiliated Hospital of Anhui Medical UniversitySchool of Basic Medical Sciences and Biopharmaceutical Research Institute, Anhui Medical UniversityImaging Center, The Third Affiliated Hospital of Anhui Medical UniversityCentral Laboratory, The First Affiliated Hospital of Anhui Medical UniversityImaging Center, The Third Affiliated Hospital of Anhui Medical UniversityImaging Center, The Third Affiliated Hospital of Anhui Medical UniversitySuzhou Institute for Advanced Research, University of Science and Technology of ChinaSchool of Basic Medical Sciences and Biopharmaceutical Research Institute, Anhui Medical UniversityImaging Center, The Third Affiliated Hospital of Anhui Medical UniversityAbstract 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.https://doi.org/10.1186/s12951-025-03107-5Autophagic fluxHepatocellular carcinomaLysosomeMRI imagingNanodrug |
| spellingShingle | Huanyu Chen Jun Liu Zhichao Cao Jiajia Li Hong Zhang Qianqian Yang Jian Cheng Yuxian Shen Kewu He Enhancing hepatocellular carcinoma therapy with DOX-loaded SiO2 nanoparticles via mTOR-TFEB pathway autophagic flux inhibition Journal of Nanobiotechnology Autophagic flux Hepatocellular carcinoma Lysosome MRI imaging Nanodrug |
| title | Enhancing hepatocellular carcinoma therapy with DOX-loaded SiO2 nanoparticles via mTOR-TFEB pathway autophagic flux inhibition |
| title_full | Enhancing hepatocellular carcinoma therapy with DOX-loaded SiO2 nanoparticles via mTOR-TFEB pathway autophagic flux inhibition |
| title_fullStr | Enhancing hepatocellular carcinoma therapy with DOX-loaded SiO2 nanoparticles via mTOR-TFEB pathway autophagic flux inhibition |
| title_full_unstemmed | Enhancing hepatocellular carcinoma therapy with DOX-loaded SiO2 nanoparticles via mTOR-TFEB pathway autophagic flux inhibition |
| title_short | Enhancing hepatocellular carcinoma therapy with DOX-loaded SiO2 nanoparticles via mTOR-TFEB pathway autophagic flux inhibition |
| title_sort | enhancing hepatocellular carcinoma therapy with dox loaded sio2 nanoparticles via mtor tfeb pathway autophagic flux inhibition |
| topic | Autophagic flux Hepatocellular carcinoma Lysosome MRI imaging Nanodrug |
| url | https://doi.org/10.1186/s12951-025-03107-5 |
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