Department of Urology, Kidney and Urology Center, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, P. R. China.
Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, P. R. China.
Biomacromolecules. 2024 Jun 10;25(6):3685-3702. doi: 10.1021/acs.biomac.4c00260. Epub 2024 May 23.
Combination therapy has emerged as a promising approach for treating tumors, although there is room for improvement. This study introduced a novel strategy that combined the enhancement of apoptosis, ferroptosis, and DNA damage to improve therapeutic outcomes for prostate cancer. Specifically, we have developed a supramolecular oxidative stress nanoamplifier, which was comprised of β-cyclodextrin, paclitaxel, and ferrocene-poly(ethylene glycol). Paclitaxel within the system disrupted microtubule dynamics, inducing G2/M phase arrest and apoptosis. Concurrently, ferrocene utilized hydrogen peroxide to generate toxic hydroxyl radicals in cells through the Fenton reaction, triggering a cascade of reactive oxygen species expansion, reduction of glutathione levels, lipid peroxidation, and ferroptosis. The increased number of hydroxyl radicals and the inhibitory effect of THZ531 on DNA repair mechanisms exacerbated DNA damage within tumor cells. As expected, the supramolecular nanoparticles demonstrated excellent drug delivery ability to tumor cells or tissues, exhibited favorable biological safety , and enhanced the killing effect on prostate cancer.
联合治疗已成为治疗肿瘤的一种有前途的方法，但仍有改进的空间。本研究介绍了一种新的策略，即将细胞凋亡、铁死亡和 DNA 损伤的增强相结合，以改善前列腺癌的治疗效果。具体来说，我们开发了一种超分子氧化应激纳米放大器，由β-环糊精、紫杉醇和二茂铁-聚乙二醇组成。该系统中的紫杉醇破坏微管动力学，诱导 G2/M 期阻滞和细胞凋亡。同时，二茂铁利用过氧化氢通过芬顿反应在细胞内产生有毒的羟基自由基，引发一系列活性氧的扩张、谷胱甘肽水平的降低、脂质过氧化和铁死亡。增加的羟基自由基数量和 THZ531 对 DNA 修复机制的抑制作用加剧了肿瘤细胞内的 DNA 损伤。正如预期的那样，超分子纳米粒子表现出对肿瘤细胞或组织的优异药物递送能力，表现出良好的生物安全性，并增强了对前列腺癌的杀伤作用。
