School of Materials Science and Engineering, Central South University, Changsha, Hunan 410083, China.
ACS Appl Mater Interfaces. 2022 Jun 29;14(25):28537-28547. doi: 10.1021/acsami.2c03975. Epub 2022 Jun 15.
The major hurdles of chemodynamic therapy (CDT) are nondegradability and low-efficiency utilization of chemodynamic agents, and intracellular glutathione (GSH)-induced rapid scavenging of hydroxyl radicals (•OH). Here, a biodegradable a-CFT@IP6@BSA agent is reported for efficient cancer therapy by encapsulating amorphous copper iron tellurite nanoparticles (a-CFT NPs) into inositol hexaphosphate (IP6) and bovine serum albumin (BSA). The biggest merits of this agent are the GSH responsive degradation and amorphous structure, allowing the tumor-specific release of plenty of Cu ions and their high-efficiency utilization for •OH production via the Fenton-like reaction. Besides, the released Cu ions can deplete the intracellular GSH and thereby protect •OH from scavenging, greatly improving the CDT efficiency. Further, it is found that the a-CFT@IP6@BSA NP treatment down-regulates the levels of glutathione peroxidase 4 and BCL-2, indicating GSH depletion-associated ferroptosis and IP6-induced apoptotic death of cancer cells. Utilizing the / dual-modal magnetic resonance imaging capability, the a-CFT@IP6@BSA NPs are demonstrated with excellent in vivo anticancer efficiency and have great potential for imaging-guided cancer treatment.
化学动力学疗法(CDT)的主要障碍是非降解性和化学动力学试剂的低效利用,以及细胞内谷胱甘肽(GSH)诱导的羟基自由基(•OH)的快速清除。在这里,报道了一种可生物降解的 a-CFT@IP6@BSA 试剂,通过将非晶态铜铁碲酸盐纳米粒子(a-CFT NPs)封装到肌醇六磷酸(IP6)和牛血清白蛋白(BSA)中,用于高效癌症治疗。该试剂的最大优点是 GSH 响应性降解和非晶态结构,允许肿瘤特异性释放大量 Cu 离子,并通过类 Fenton 反应高效利用它们来产生 •OH。此外,释放的 Cu 离子可以耗尽细胞内的 GSH,从而防止 •OH 被清除,大大提高了 CDT 的效率。此外,研究发现,a-CFT@IP6@BSA NP 处理下调谷胱甘肽过氧化物酶 4 和 BCL-2 的水平,表明 GSH 耗竭相关的铁死亡和 IP6 诱导的癌细胞凋亡死亡。利用双模态磁共振成像能力,证明了 a-CFT@IP6@BSA NPs 具有优异的体内抗癌效率,在成像引导癌症治疗方面具有巨大的潜力。