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Co-delivery of Salinomycin and Curcumin for Cancer Stem Cell Treatment by Inhibition of Cell Proliferation, Cell Cycle Arrest, and Epithelial–Mesenchymal Transition
Frontiers in Chemistry ( IF 3.8 ) Pub Date : 2020-11-09 , DOI: 10.3389/fchem.2020.601649
Yongmei Zhao , Kaikai Wang , Yuanlin Zheng , Xiaobao Zeng , Yi Chieh Lim , Tianqing Liu

Malignant cancer is a devastating disease often associated with a poor clinical prognosis. For decades, modern drug discoveries have attempted to identify potential modulators that can impede tumor growth. Cancer stem cells however are more resistant to therapeutic intervention, which often leads to treatment failure and subsequent disease recurrence. Here in this study, we have developed a specific multi-target drug delivery nanoparticle system against breast cancer stem cells (BCSCs). Therapeutic agents curcumin and salinomycin have complementary functions of limiting therapeutic resistance and eliciting cellular death, respectively. By conjugation of CD44 cell-surface glycoprotein with poly(lactic-co-glycolic acid) (PLGA) nanoparticles that are loaded with curcumin and salinomycin, we investigated the cellular uptake of BCSCs, drug release, and therapeutic efficacy against BCSCs. We determined CD44-targeting co-delivery nanoparticles are highly efficacious against BCSCs by inducing G1 cell cycle arrest and limiting epithelial–mesenchymal transition. This curcumin and salinomycin co-delivery system can be an efficient treatment approach to target malignant cancer without the repercussion of disease recurrence.



中文翻译:

通过抑制细胞增殖,抑制细胞周期阻滞和上皮-间质转化,共同提供沙利霉素和姜黄素治疗癌症干细胞

恶性肿瘤是一种破坏性疾病,通常与不良的临床预后相关。数十年来,现代药物发现已尝试鉴定出可能阻碍肿瘤生长的潜在调节剂。然而,癌症干细胞对治疗干预更具抵抗力,这通常会导致治疗失败和随后的疾病复发。在本研究中,我们已经开发出针对乳腺癌干细胞(BCSC)的特定的多目标药物递送纳米颗粒系统。姜黄素和沙利霉素的治疗剂具有互补的功能,分别限制了治疗抵抗力和引起细胞死亡。通过将CD44细胞表面糖蛋白与载有姜黄素和沙利霉素的聚乳酸-乙醇酸(PLGA)纳米粒子结合,我们研究了BCSCs的细胞摄取,药物释放,和针对BCSC的治疗功效。我们确定了靶向CD44的共递送纳米颗粒通过诱导G对抗BCSC具有很高的功效1细胞周期停滞和限制上皮-间质转化。该姜黄素和沙利霉素共同递送系统可以是靶向恶性肿瘤的有效治疗方法,而不会影响疾病复发。

更新日期:2021-01-16
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