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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Gu, Liwei Zhang, Jiaxing Liu, Dandan Chen, Jiayun Liu, Shuzhi Peng, Qing Tian, Ya Du, Maobo Zhang, Junzhe Xiao, Wei Shen, Shuo Wang, Jigang |
| Abstract | Breast cancer is the leading cause of cancer-related deaths in women and remains a formidable therapeutic challenge. Mitochondria participate in a myriad of essential cellular processes, such as metabolism, and are becoming an ideal target for cancer therapy. Artemisinin and its derivatives have demonstrated multiple activities in the context of various cancers. Mitochondrial autophagy(mitophagy) is one of the important anti-tumor mechanisms of artemisinin drugs. However, the lack of specific tumor targeting ability limits the anti-tumor efficacy of artemisinin drugs. In this study, a GSH-sensitive artesunate smart conjugate (TPP-SS-ATS) was synthesized and liposomes (TPP-SS-ATS-LS) that target tumor cells and mitochondria were further prepared. The advantages of TPP-SS-ATS-LS targeting to the breast tumor were verified by in vivo and in vitro evaluations. In our study, the cytotoxicity was obviously enhanced in vitro and tumor growth inhibition rate was increased from 37.7% to 56.4% at equivalent artesunate dosage in breast cancer orthotopic implanted mice. Meanwhile, mitochondrial dysfunction, suppression of ATP production and respiratory capacity were detected in breast cancer cells. We further discovered that TPP-SS-ATS-LS inhibited tumor cells proliferation through mitophagy by regulating PHB2 and PINK1 expression. These results provide new research strategies for the development of new artemisinin-based anti-tumor drugs. |
| Related Links | https://jnanobiotechnology.biomedcentral.com/counter/pdf/10.1186/s12951-022-01569-5.pdf |
| Ending Page | 21 |
| Page Count | 21 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 14773155 |
| DOI | 10.1186/s12951-022-01569-5 |
| Journal | Journal of Nanobiotechnology |
| Issue Number | 1 |
| Volume Number | 20 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2022-08-13 |
| Access Restriction | Open |
| Subject Keyword | Biotechnology Nanotechnology Molecular Medicine Artesunate smart conjugate Mitochondrial targeting Liposomes Anti-tumor Mitophagy |
| Content Type | Text |
| Resource Type | Article |
| Subject | Bioengineering Pharmaceutical Science Medicine Applied Microbiology and Biotechnology Biomedical Engineering Molecular Medicine Nanoscience and Nanotechnology |
| Journal Impact Factor | 10.6/2023 |
| 5-Year Journal Impact Factor | 11.4/2023 |
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