Sun Yunhao, Ying Kaijun, Sun Jian, Qiu Limin, Wang Yao, Ji Mingming, Zhou Lulu, Chen Jinjin
Department of Thoracic Surgery, The First People's Hospital of Yancheng City, The Yancheng Clinical College of Xuzhou Medical University, Yancheng, 224005, Jiangsu, People's Republic of China.
School of Perfume and Aroma Technology, Shanghai Institute of Technology, Shanghai, 201418, People's Republic of China.
Discov Nano. 2024 Dec 11;19(1):200. doi: 10.1186/s11671-024-04168-5.
Cisplatin (CDDP) is the primary drug used in the initial treatment of esophageal cancer (EC). However, its side effects and resistance can limit its effectiveness in clinical therapy. Curcumin (Cur)-mediated glutathione (GSH) depletion can reverse resistance, enhance the chemosensitivity of CDDP, and further improve the efficacy of platinum-containing chemotherapy in the treatment of esophageal cancer. However, it is also faced with problems of poor water solubility and low bioavailability in vivo, which severely hinders cancer treatments. In order to address these issues, we developed a novel nanotherapeutic system called CDCZA, combining Cur/CDDP/Cu/ZIF8@Au to enhance chemotherapy through GSH depletion and chemodynamic therapy through self-produced HO. Cu and CDDP were precisely co-loaded into Cu/ZIF8 nanoparticles using a one-pot method, then ultra-small gold nanoparticles mimicking glucose oxidase (Au nanoparticles) were embedded in the outer shell to create the CDCZA nano system. The released Cur could notably decrease intracellular GSH content and thus improve the chemosensitivity of CDDP, resulting in severe cellular apoptosis. And the Au nanoparticles effectively enabled chemodynamic therapy enhancement by accelerating the depletion of β-D-glucose into HO. As a result, the CDCZA nanoparticles showed increased tumor accumulation and improved antitumor effectiveness in a model of EC. Taken together, this work provides a new idea for the clinical design of efficient treatment reagents for EC.
顺铂（CDDP）是食管癌（EC）初始治疗中使用的主要药物。然而，其副作用和耐药性会限制其在临床治疗中的有效性。姜黄素（Cur）介导的谷胱甘肽（GSH）消耗可逆转耐药性，增强CDDP的化学敏感性，并进一步提高含铂化疗在食管癌治疗中的疗效。然而，它也面临着水溶性差和体内生物利用度低的问题，这严重阻碍了癌症治疗。为了解决这些问题，我们开发了一种名为CDCZA的新型纳米治疗系统，将Cur/CDDP/Cu/ZIF8@Au结合起来，通过GSH消耗增强化疗，并通过自身产生的HO进行化学动力学治疗。采用一锅法将Cu和CDDP精确共负载到Cu/ZIF8纳米颗粒中，然后将模拟葡萄糖氧化酶的超小金纳米颗粒（Au纳米颗粒）嵌入外壳中，构建CDCZA纳米系统。释放的Cur可显著降低细胞内GSH含量，从而提高CDDP的化学敏感性，导致严重的细胞凋亡。并且Au纳米颗粒通过加速β-D-葡萄糖消耗为HO有效地增强了化学动力学治疗。结果，CDCZA纳米颗粒在EC模型中显示出增加的肿瘤蓄积和提高的抗肿瘤效果。综上所述，这项工作为食管癌高效治疗试剂的临床设计提供了新思路。
