Pharmacological ascorbate potentiates combination nanomedicines and reduces cancer cell stemness to prevent post-surgery recurrence and systemic metastasis.

Pharmacological ascorbate potentiates combination nanomedicines and reduces cancer cell stemness to prevent post-surgery recurrence and systemic metastasis.
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药理学抗坏血酸可增强组合纳米药物的作用并减少癌细胞干性,以防止术后复发和全身转移。

DOI:
10.1016/j.biomaterials.2023.122037
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发表时间:
2023
期刊:
影响因子:
14
通讯作者:
Lin,Wenbin
Lin,Wenbin
中科院分区:
工程技术1区
文献类型:
--
作者:
Jiang,Xiaomin;Liu,Jianqiao;Mao,Jianming;Han,Wenbo;Fan,Yingjie;Luo,Taokun;Xia,Junjie;Lee,MortenJ;Lin,Wenbin

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常规化疗靶向增殖性癌细胞以阻止肿瘤进展或使肿瘤消退。然而,肿瘤细胞的可塑性使其表型变化获得化疗抗性,导致治疗失败或成功治疗后肿瘤复发。在这里,我们报告了使用高剂量药理学抗坏血酸盐来增强纳米级配位聚合物(NCP)的治疗功效,提供两种临床化疗药物(卡铂/多西他赛和奥沙利铂/SN 38)组合,并针对肿瘤细胞的代谢可塑性。高剂量抗坏血酸和NCP的组合治疗通过显著降低实体瘤中癌症干细胞(CSC)的丰度来克服多药耐药性,如肿瘤多能性因子的表达降低所证明的。在多种小鼠癌症模型中,CSC的清除抑制了手术后复发和全身转移。
Conventional chemotherapy targets proliferative cancer cells to halt tumor progression or regress tumors. However, the plasticity of tumor cells enables their phenotypical changes to acquire chemo-resistance, leading to treatment failure or tumor recurrence after a successful treatment course. Here, we report the use of high-dose pharmacologic ascorbate to potentiate treatment efficacy of nanoscale coordination polymers (NCPs) delivering two clinical combinations of chemotherapeutics, carboplatin/docetaxel and oxaliplatin/SN38, and to target metabolic plasticity of tumor cells. Combination treatments of high-dose ascorbate and NCPs overcome multi-drug resistance by significantly reducing the abundance of cancer stem cells (CSCs) in solid tumors, as evidenced by reduced expression of tumor pluripotency factors. The clearance of CSCs inhibits post-surgery recurrence and systemic metastasis in multiple mouse models of cancer.
幽门螺杆菌脂多糖抑制胃粘膜层粘连蛋白受体。
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