吉西他滨
胰腺癌
核苷酸还原酶
癌症研究
医学
微泡
去铁斯若
药品
药物输送
癌症
药理学
化学
内科学
小RNA
蛋白质亚单位
生物化学
有机化学
基因
地中海贫血
作者
Yongmei Zhao,Yuan‐Lin Zheng,Yan Zhu,Yi Zhang,Hongyan Zhu,Tianqing Liu
出处
期刊:Pharmaceutics
[MDPI AG]
日期:2021-09-17
卷期号:13 (9): 1493-1493
被引量:58
标识
DOI:10.3390/pharmaceutics13091493
摘要
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.
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