谷胱甘肽
前药
奥沙利铂
结直肠癌
敏化
前列腺素E2
药理学
化疗
化学
细胞凋亡
癌症研究
炎症
癌症
医学
生物化学
内科学
免疫学
酶
作者
Wenjia Wang,Xingyue He,Xiaojie Wang,Tao Zhao,Osamu Muraoka,Genzoh Tanabe,Weijia Xie,Tian‐Jiao Zhou,Xing Liu,Qing‐Ri Jin,Hu‐Lin Jiang
标识
DOI:10.1016/j.cclet.2023.108656
摘要
Oxaliplatin (Oxa) is the first-line chemotherapeutic drug for the treatment of colorectal cancer (CRC). However, long-term Oxa chemotherapy can induce inflammation and increase the levels of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2), which can promote tumor metastasis. Moreover, high glutathione (GSH) levels in CRC cells significantly reduce Oxa sensitivity and seriously restrict the clinical application of Oxa. Herein, an Oxa (IV) prodrug with anti-inflammatory properties (desmethyl naproxe, DN) and GSH-depleting cyclodextrin pseudo-polyrotaxane carriers were prepared and further self-assembled into micellar nanoparticles (designated DNPt@PPRI). The relesae of DN from DNPt@PPRI can reduce the level of PGE2 to inhibit inflammation and tumor metastasis by decreasing COX-2 protein, and also synergize with Oxa to inhibit tumor. More importantly, GSH depletion can reduce the detoxification of Oxa and further enhance chemotherapy-induced apoptosis. DNPt@PPRI have a good GSH depletion ability to enhance the sensitivity of Oxa, indicating a potential in the synergistic chemotherapy and chemo-sensitization of colorectal cancer.
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