Synergistic Effect of Layered Double Hydroxides Nanodosage Form to Induce Apoptosis and Ferroptosis in Breast Cancer.

Background: 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. Methods: 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. Results: 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. Conclusion: 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.

The addition of organic fertilizer can reduce the dependence of dryland yield on rainfall-based on a 32-year long-term study.

Clarifying the synergistic effect between rainfall and fertilization in rainfed farming and joint effect on crop yield can provide theoretical basis for improving the sustainable productivity of farmland in dry farming. A 32-year fertilizer regulation experiment was conducted in the dry farming region of the Loess Plateau. According to the precipitation, it was divided into dry, normal and high rainfall years. The influence of long-term fertilization regulation on crop yield and farmland moisture changes under different rainfall years was analyzed, and the regulation mechanism of fertilization and precipitation coordination on crop yield under different rainfall years was explored. The results showed that effects of fertilization on crop yield and water use efficiency (WUE) were closely related to experimental years. In the early stage, the increase in treatments with higher amounts of nitrogen was more significant, while in the later stage, the increase in treatments with less organic fertilizer was more significant. The correlation of crop yield, the whole rainfall (WR), growth period rainfall (GPR), fallow period rainfall (FPR), water storage during sowing (SWS), evapotranspiration (ET), WUE and utilization efficiency of precipitation (PUE)under different rainfall years and treatments was analyzed. The results showed that the crop yield showed that the correlation with PUE showed high> dry> normal rainfall year, and the correlation with WUE showed the law of dry> high> normal rainfall year. The correlation of organic fertilizer treatments was lower than that of single chemical fertilizer. With the years extension of application organic fertilizer, application low amount of organic fertilizer can improve crop yield by improving PUE, and can achieve the effect of application high amount of organic fertilizer. No matter what the rainfall years, the long-term application of organic fertilizer can make full use of the rainfall to improve the WUE, and then ensure the sustainability of crop yield.