M1 Macrophage-Derived Exosomes Loaded with Gemcitabine and Deferasirox against Chemoresistant Pancreatic Cancer
Pancreatic cancer is a malignant disease with high mortality and poor prognosis due to lack of early diagnosis and low treatment efficiency after diagnosis. Although Gemcitabine (GEM) is used as the first-line chemotherapeutic drug, chemoresistance is still the major problem that limits its therapeu...
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| Format: | Article |
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MDPI AG
2021-09-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/9/1493 |
| _version_ | 1829091507030720512 |
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| author | Yongmei Zhao Yuanlin Zheng Yan Zhu Yi Zhang Hongyan Zhu Tianqing Liu |
| author_facet | Yongmei Zhao Yuanlin Zheng Yan Zhu Yi Zhang Hongyan Zhu Tianqing Liu |
| author_sort | Yongmei Zhao |
| collection | DOAJ |
| description | Pancreatic cancer is a malignant disease with high mortality and poor prognosis due to lack of early diagnosis and low treatment efficiency after diagnosis. Although Gemcitabine (GEM) is used as the first-line chemotherapeutic drug, chemoresistance is still the major problem that limits its therapeutic efficacy. Here in this study, we developed a specific M1 macrophage-derived exosome (M1Exo)-based drug delivery system against GEM resistance in pancreatic cancer. In addition to GEM, Deferasirox (DFX) was also loaded into drug carrier, M1Exo, in order to inhibit ribonucleotide reductase regulatory subunit M2 (RRM2) expression via depleting iron, and thus increase chemosensitivity of GEM. The M1Exo nanoformulations combining both GEM and DFX significantly enhanced the therapeutic efficacy on the GEM-resistant PANC-1/GEM cells and 3D tumor spheroids by inhibiting cancer cell proliferation, cell attachment and migration, and chemoresistance to GEM. These data demonstrated that M1Exo loaded with GEM and DFX offered an efficient therapeutic strategy for drug-resistant pancreatic cancer. |
| first_indexed | 2024-03-10T07:18:23Z |
| format | Article |
| id | doaj.art-7bccbbf6b74149d1a2f8f7fc6870f2bb |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T07:18:23Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-7bccbbf6b74149d1a2f8f7fc6870f2bb2023-11-22T14:48:35ZengMDPI AGPharmaceutics1999-49232021-09-01139149310.3390/pharmaceutics13091493M1 Macrophage-Derived Exosomes Loaded with Gemcitabine and Deferasirox against Chemoresistant Pancreatic CancerYongmei Zhao0Yuanlin Zheng1Yan Zhu2Yi Zhang3Hongyan Zhu4Tianqing Liu5School of Pharmacy, Nantong University, Nantong 226019, ChinaSchool of Pharmacy, Nantong University, Nantong 226019, ChinaSchool of Pharmacy, Nantong University, Nantong 226019, ChinaSchool of Chemistry, University of Glasgow, Glasgow G12 8QQ, UKSchool of Pharmacy, Nantong University, Nantong 226019, ChinaNICM Health Research Institute, Western Sydney University, Sydney, NSW 2145, AustraliaPancreatic cancer is a malignant disease with high mortality and poor prognosis due to lack of early diagnosis and low treatment efficiency after diagnosis. Although Gemcitabine (GEM) is used as the first-line chemotherapeutic drug, chemoresistance is still the major problem that limits its therapeutic efficacy. Here in this study, we developed a specific M1 macrophage-derived exosome (M1Exo)-based drug delivery system against GEM resistance in pancreatic cancer. In addition to GEM, Deferasirox (DFX) was also loaded into drug carrier, M1Exo, in order to inhibit ribonucleotide reductase regulatory subunit M2 (RRM2) expression via depleting iron, and thus increase chemosensitivity of GEM. The M1Exo nanoformulations combining both GEM and DFX significantly enhanced the therapeutic efficacy on the GEM-resistant PANC-1/GEM cells and 3D tumor spheroids by inhibiting cancer cell proliferation, cell attachment and migration, and chemoresistance to GEM. These data demonstrated that M1Exo loaded with GEM and DFX offered an efficient therapeutic strategy for drug-resistant pancreatic cancer.https://www.mdpi.com/1999-4923/13/9/1493exosomesgemcitabinedeferasiroxpancreatic cancerchemoresistanceRRM2 |
| spellingShingle | Yongmei Zhao Yuanlin Zheng Yan Zhu Yi Zhang Hongyan Zhu Tianqing Liu M1 Macrophage-Derived Exosomes Loaded with Gemcitabine and Deferasirox against Chemoresistant Pancreatic Cancer Pharmaceutics exosomes gemcitabine deferasirox pancreatic cancer chemoresistance RRM2 |
| title | M1 Macrophage-Derived Exosomes Loaded with Gemcitabine and Deferasirox against Chemoresistant Pancreatic Cancer |
| title_full | M1 Macrophage-Derived Exosomes Loaded with Gemcitabine and Deferasirox against Chemoresistant Pancreatic Cancer |
| title_fullStr | M1 Macrophage-Derived Exosomes Loaded with Gemcitabine and Deferasirox against Chemoresistant Pancreatic Cancer |
| title_full_unstemmed | M1 Macrophage-Derived Exosomes Loaded with Gemcitabine and Deferasirox against Chemoresistant Pancreatic Cancer |
| title_short | M1 Macrophage-Derived Exosomes Loaded with Gemcitabine and Deferasirox against Chemoresistant Pancreatic Cancer |
| title_sort | m1 macrophage derived exosomes loaded with gemcitabine and deferasirox against chemoresistant pancreatic cancer |
| topic | exosomes gemcitabine deferasirox pancreatic cancer chemoresistance RRM2 |
| url | https://www.mdpi.com/1999-4923/13/9/1493 |
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