Chen Wei Jun, Gupta Dhanu, Yang Meiyang, Yang Fuwei, Feng Ning, Song Junling, Wood Matthew J A, Qiu Lipeng, Chen Jinghua
School of Life Sciences and Health Engineering, Jiangnan University, Wuxi, 214122, China.
School of Chemical and Material Engineering, Jiangnan University, Wuxi, 214122, China.
Small. 2023 Dec;19(50):e2303403. doi: 10.1002/smll.202303403. Epub 2023 Aug 30.
Metal-organic frameworks (MOFs) have emerged as promising novel therapeutics for treating malignancies due to their tunable porosity, biocompatibility, and modularity to functionalize with various chemotherapeutics drugs. However, the design and synthesis of dual-stimuli responsive MOFs for controlled drug release in tumor microenvironments are vitally essential but still challenging. Meanwhile, the catalytic effect of metal ions selection and ratio optimization in MOFs for enhanced chemodynamic therapy (CDT) is relatively unexplored. Herein, a series of MnFe-based MOFs with pH/glutathione (GSH)-sensitivity are synthesized and then combined with gold nanoparticles (Au NPs) and cisplatin prodrugs (DSCP) as a cascade nanoreactor (SMnFeCGH) for chemo-chemodynamic-starvation synergistic therapy. H and GSH can specifically activate the optimal SMnFeCGH nanoparticles in cancer cells to release Mn /Fe , Au NPs, and DSCP rapidly. The optimal ratio of Mn/Fe shows excellent H O decomposition efficiency for accelerating CDT. Au NPs can cut off the energy supply to cancer cells for starvation therapy and strengthen CDT by providing large amounts of H O . Then H O is catalyzed by Mn /Fe to generate highly toxic •OH with the depletion of GSH. Meanwhile, the reduced DSCP accelerates cancer cell regression for chemotherapy. The ultrasensitivity cascade nanoreactor can enhance the anticancer therapeutic effect by combining chemotherapy, CDT, and starvation therapy.
金属有机框架（MOFs）因其可调的孔隙率、生物相容性以及与各种化疗药物功能化的模块化特性，已成为治疗恶性肿瘤的有前景的新型疗法。然而，设计和合成用于在肿瘤微环境中实现可控药物释放的双刺激响应性MOFs至关重要，但仍具有挑战性。同时，MOFs中金属离子选择和比例优化对增强化学动力学疗法（CDT）的催化作用尚未得到充分探索。在此，合成了一系列具有pH/谷胱甘肽（GSH）敏感性的MnFe基MOFs，然后将其与金纳米颗粒（Au NPs）和顺铂前药（DSCP）结合，作为级联纳米反应器（SMnFeCGH）用于化学-化学动力学-饥饿协同治疗。H⁺和GSH可特异性激活癌细胞中的最佳SMnFeCGH纳米颗粒，迅速释放Mn²⁺/Fe²⁺、Au NPs和DSCP。Mn/Fe的最佳比例显示出优异的H₂O₂分解效率，可加速CDT。Au NPs可切断癌细胞的能量供应以进行饥饿治疗，并通过提供大量H₂O₂增强CDT。然后H₂O₂在Mn²⁺/Fe²⁺催化下，随着GSH的消耗产生高毒性的•OH。同时，还原的DSCP加速癌细胞消退以进行化疗。这种超灵敏级联纳米反应器可通过结合化疗、CDT和饥饿疗法增强抗癌治疗效果。
