Jiang Ying, Lu Hao, Lei Lingli, Scherman Daniel, Liu Yingshuai
Key Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education, School of Materials and Energy, Southwest University, Chongqing 400715, China; Department of Mechanics and Engineering Science, Beijing Innovation Centre for Engineering Science and Advanced Technology, College of Engineering, Peking University, Beijing 100871, China.
Key Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education, School of Materials and Energy, Southwest University, Chongqing 400715, China.
J Colloid Interface Sci. 2025 Dec 15;700(Pt 1):138342. doi: 10.1016/j.jcis.2025.138342. Epub 2025 Jul 5.
The design of nanomedicines targeting specific tumor microenvironment (TME) characteristics, such as low pH, hypoxia, and elevated glutathione (GSH) concentration, holds significant potential for selectively killing cancer cells. In this study, we have developed a TME-responsive nanoparticle, i.e., MIL-53(Fe)@MnO stabilized with polyethylene glycol (FMP), which is capable of depleting GSH and sustainably generating hydroxyl radical (•OH) for enhanced chemodynamic therapy of cancer. After endocytosis, the FMP nanoparticles undergo gradual decomposition, resulting in GSH depletion while releasing Fenton-active Fe and Mn ions. These ions then subsequently catalyze a Fenton-like reaction to generate highly toxic •OH, ultimately inducing oxidative cell death. As a synergistic effect, the depletion of GSH further enhances therapeutic efficacy by inhibiting intracellular •OH scavenging. In vivo experiments demonstrated that this synergistically chemotherapeutic approach efficiently suppressed tumor growth without inducing significant systemic toxicity. This work presents a promising nanotherapeutic strategy that simultaneously depletes intracellular GSH and sustains cytotoxic •OH generation for enhanced tumor treatment.
针对特定肿瘤微环境（TME）特征（如低pH值、缺氧和谷胱甘肽（GSH）浓度升高）设计的纳米药物，在选择性杀死癌细胞方面具有巨大潜力。在本研究中，我们开发了一种TME响应性纳米颗粒，即聚乙二醇稳定的MIL-53(Fe)@MnO（FMP），它能够消耗GSH并可持续地产生羟基自由基（•OH），以增强癌症的化学动力学治疗。内吞后，FMP纳米颗粒逐渐分解，导致GSH消耗，同时释放具有芬顿活性的铁和锰离子。这些离子随后催化类芬顿反应生成剧毒的•OH，最终诱导细胞氧化死亡。作为一种协同效应，GSH的消耗通过抑制细胞内•OH清除进一步增强治疗效果。体内实验表明，这种协同化疗方法能有效抑制肿瘤生长，且不会引起明显的全身毒性。这项工作提出了一种有前景的纳米治疗策略，即同时消耗细胞内GSH并持续产生细胞毒性•OH以增强肿瘤治疗效果。
