Inducing cancer cell death has always been a research hotspot in life sciences. With the continuous deepening and diversification of related research, the potential value of metal elements in inducing cell death has been explored. Taking iron as an example, ferroptosis, mainly characterized by increasing iron load and driving the production of large amounts of lipid peroxides and eventually leading to cell death, has recently attracted great interest in the cancer research community. After iron, copper, a trace element, has received extensive attention in cell death, especially in inducing tumor cell death. Copper and its complexes can induce autophagy or apoptosis in tumor cells through a variety of different mechanisms of action (activation of stress pathways, arrest of cell cycle, inhibition of angiogenesis, cuproptosis, and paraptosis), which are promising in cancer therapy and have become new hotspots in cancer treatment research. This article reviews the main mechanisms and potential applications of novel copper and copper compound-induced cell death, focusing on copper compounds and their anticancer applications.
Breast cancer is among the most common fatal diseases among women. Low-toxicity apigenin (AGN) is of interest due to its good antitumor activity, but its clinical application is severely limited due to its poor water solubility and low bioavailability. An effective strategy to enhance the anti-breast-cancer activity of AGN is to develop it as a nanodelivery system. Silk fibroin (SF) is an ideal drug carrier with good biocompatibility, biodegradability, and a simple extraction process. This paper develops a novel and efficient apigenin-loaded silk fibroin nanodelivery system (SF-AGN) by nanoprecipitation with SF as a carrier. The system was characterized in terms of morphology, zeta potential, particle size, ultraviolet (UV), infrared (IR), and synchronous thermal analyses (TG-DSC), and the in vitro cytotoxicity and in vivo pharmacokinetics were examined. Finally, the chronic toxicity of SF-AGN in mice was studied. The SF-AGN nanodelivery system has good dispersibility, a hydrated particle size of 163.35 nm, a zeta potential of −18.5 mV, an average drug loading of 6.20%, and good thermal stability. MTT studies showed that SF-AGN significantly enhanced the inhibitory effect of AGN on 4T1 and MDA-MB-231 cells. Pharmacokinetic studies have demonstrated that SF-AGN can dramatically improve the bioavailability of AGN. The results of toxicity experiments showed that SF-AGN is biocompatible and does not alter normal tissues or organs. In sum, the SF-AGN nanodelivery system is a promising drug-delivery system for the clinical treatment of breast cancer.
The development of inorganic antibacterial agents that impart antibacterial properties to biomaterials has attracted widely attention. The paper introduced a kind of hybrid nanosphere antibacterial agent composed of wheat gliadin (WG) and zinc oxide (ZnO), with antibacterial effecacy and low toxicity. The ZnO/WG hybrid nanospheres were environment-friendly integrated by molecular self-assembly co-precipitating and freeze-drying transformating, and were characterized using X-ray diffraction (XRD), Fourier Transform infrared spectroscopy (FTIR), Scanning electron microscope (SEM), Atomic absorption spectroscopy (AAS), bacteriostasis test and safety evaluation. It was found that the prepared hybrid nanospheres were composed of two components, ZnO and wheat gliadin, with a diameter scope of 100~200 nm. The content of ZnO in the hybrid nanospheres can reach 46.9~70.2% (w/w); The anti-bacteria tests proved that the prepared ZnO/WG nanospheres (containing 70% ZnO) have an significant inhibitory effect on E. coli (E.C.) and Staphylococcus aureus(S.A.) while the suspension concentration of the nanospheres was above 5 mg/mL. Furthermore, the ZnO/WG nanospheres are relatively safe and highly effective in cells and mice. Therefore, the prepared novel ZnO/WG hybrid nanospheres were supposed to apply in the preparation of anti-infective wound dressings, tissue engineering skin scaffold materials, food and cosmetics preservatives, and so on.
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