Enhanced Sensitivity of Tumor Cells to Autophagy Inhibitors Using Fasting-Mimicking Diet and Targeted Lysosomal Delivery Nanoplatform
Autophagy is one of the key pathways for tumor cell survival and proliferation. Therefore, inhibition of autophagy has been extensively studied for cancer therapy. However, current autophagy inhibitors lack specificity and are ineffective in limiting tumor progression. Herein, we report a nanoplatform for tumor-site-targeted delivery of hydroxychloroquine (HCQ) using insulin-like growth factors 2 receptor (IGF2R)-targeted liposomes (iLipo-H). A fasting-mimicking diet (FMD) is used to increase the autophagy levels in tumor cells, thereby increasing the sensitivity of tumor cells to HCQ. In addition, FMD treatment upregulates the expression of IGF2R in tumor cells, but not normal cells. Consequently, iLipo-H nanoparticles efficiently accumulate at the tumor site under FMD condition. In vivo studies demonstrate that iLipo-H nanoparticles efficiently inhibit 4T1 tumor growth without obvious side effects, especially under FMD condition. This study provides a promising strategy to increase the sensitivity of tumor cells to autophagy inhibitors for effective cancer therapy.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:22 |
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| Enthalten in: |
Nano letters - 22(2022), 22 vom: 23. Nov., Seite 9154-9162 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Qian, Ruihao [VerfasserIn] |
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| Links: |
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| Themen: |
4QWG6N8QKH |
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| Anmerkungen: |
Date Completed 24.11.2022 Date Revised 06.01.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1021/acs.nanolett.2c03890 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM348562543 |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Autophagy is one of the key pathways for tumor cell survival and proliferation. Therefore, inhibition of autophagy has been extensively studied for cancer therapy. However, current autophagy inhibitors lack specificity and are ineffective in limiting tumor progression. Herein, we report a nanoplatform for tumor-site-targeted delivery of hydroxychloroquine (HCQ) using insulin-like growth factors 2 receptor (IGF2R)-targeted liposomes (iLipo-H). A fasting-mimicking diet (FMD) is used to increase the autophagy levels in tumor cells, thereby increasing the sensitivity of tumor cells to HCQ. In addition, FMD treatment upregulates the expression of IGF2R in tumor cells, but not normal cells. Consequently, iLipo-H nanoparticles efficiently accumulate at the tumor site under FMD condition. In vivo studies demonstrate that iLipo-H nanoparticles efficiently inhibit 4T1 tumor growth without obvious side effects, especially under FMD condition. This study provides a promising strategy to increase the sensitivity of tumor cells to autophagy inhibitors for effective cancer therapy | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a autophagy | |
| 650 | 4 | |a hydroxychloroquine | |
| 650 | 4 | |a insulin-like growth factors 2 receptor | |
| 650 | 4 | |a targeted delivery | |
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| 700 | 1 | |a Su, Wen |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Yue |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Haohao |e verfasserin |4 aut | |
| 700 | 1 | |a Jia, Fuhao |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Hai |e verfasserin |4 aut | |
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