乳腺癌是女性最常见的癌症,也是全球癌症死亡的主要原因之一。Ferroptosis,一种有希望的杀死癌细胞的机制,已成为肿瘤治疗的研究热点。辛伐他汀(SIM),作为一种潜在的新型抗乳腺癌药物,已被证明可引起癌细胞的铁凋亡并抑制乳腺癌的转移和复发。这项研究的目的是开发一种用于协同癌症治疗的新策略来增强铁的级联反应。
■在本文中,通过水热共沉淀法合成了铁碱形式的层状双氢氧化物负载辛伐他汀(LDHs-SIM)。通过各种分析技术评估LDHs-SIM的表征,包括紫外可见(UV-vis)光谱,X射线衍射(XRD)傅里叶变换红外(FTIR)光谱,和透射电子显微镜(TEM)。生物活性,通过体内和体外分析,分析了铁死亡机制和生物相容性,从而评价其对乳腺癌的治疗效果。
■构建的LDHs-SIM纳米系统不仅可以通过甲羟戊酸(MVA)途径释放SIM,抑制谷胱甘肽过氧化物酶4(GPX4)的表达,抑制SLC7A11的表达,降低GSH的合成效率,而且还通过Fe3+的释放促进Fe2+在细胞中的积累,并增加细胞内ROS含量。此外,LDHs-SIM纳米系统能在一定程度上诱导乳腺癌细胞凋亡,并达到凋亡和铁凋亡的协同作用。
■在本研究中,我们证明,纳米粒子的层状双氢氧化物(LDHs)装载辛伐他汀比游离药物更有效地抑制乳腺癌细胞的生长,此外,优越的抗癌治疗效果,几乎没有全身毒性,表明LDHs-SIM可以作为铁凋亡-凋亡联合抗癌治疗的安全和高性能平台。
UNASSIGNED: Breast cancer is the most common cancer in women and one of the leading causes of cancer death worldwide. Ferroptosis, a promising mechanism of killing cancer cells, has become a research hotspot in cancer therapy. Simvastatin (SIM), as a potential new anti-breast cancer drug, has been shown to cause ferroptosis of cancer cells and inhibit breast cancer metastasis and recurrence. The purpose of this study is to develop a novel strategy boosting ferroptotic cascade for synergistic cancer therapy.
UNASSIGNED: In this paper, iron base form of layered double hydroxide supported simvastatin (LDHs-SIM) was synthesized by hydrothermal co-precipitation method. The characterization of LDHs-SIM were assessed by various analytical techniques, including ultraviolet-visible (UV-vis) spectroscopy, X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, and transmission electron microscopy (TEM). Biological activity, ferroptosis mechanism and biocompatibility were analyzed through in vivo and in vitro analysis, so as to evaluate its therapeutic effect on breast cancer.
UNASSIGNED: The constructed LDHs-SIM nanosystem can not only release SIM through mevalonate (MVA) pathway, inhibit the expression of glutathione peroxidase 4 (GPX4), inhibit the expression of SLC7A11 and reduce the synthesis efficiency of GSH, but also promote the accumulation of Fe2+ in cells through the release of Fe3+, and increase the intracellular ROS content. In addition, LDHs-SIM nanosystem can induce apoptosis of breast cancer cells to a certain extent, and achieve the synergistic effect of apoptosis and ferroptosis.
UNASSIGNED: In the present study, we demonstrated that nanoparticles of layered double hydroxides (LDHs) loaded with simvastatin were more effective than a free drug at inhibiting breast cancer cell growth, In addition, superior anticancer therapeutic effects were achieved with little systemic toxicity, indicating that LDHs-SIM could serve as a safe and high-performance platform for ferroptosis-apoptosis combined anticancer therapy.