A Purposefully Designed pH/GSH‐Responsive MnFe‐Based Metal‐Organic Frameworks as Cascade Nanoreactor for Enhanced Chemo‐Chemodynamic‐Starvation Synergistic Therapy

• Published in: Small (Weinheim an der Bergstrasse, Germany) Vol. 19; no. 50; pp. e2303403 - n/a
• Main Authors: Chen, Wei Jun, Gupta, Dhanu, Yang, Meiyang, Yang, Fuwei, Feng, Ning, Song, Junling, Wood, Matthew J. A., Qiu, Lipeng, Chen, Jinghua
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.12.2023
• Subjects: Anticancer properties; Biocompatibility; Cancer; cascade nanoreactors; Cell Line, Tumor; chemodynamic therapy; Chemotherapy; Ferrous ions; Glutathione; Gold; Humans; Hydrogen Peroxide; Hydrogen-Ion Concentration; Manganese; Metal Nanoparticles; Metal-Organic Frameworks; metals ratio optimization; Modularity; Nanoparticles; Nanotechnology; Neoplasms - drug therapy; pH/GSH‐responsive; Tumor Microenvironment; cascade nanoreactors; chemodynamic therapy; pH/GSH-responsive; metal-organic frameworks; metals ratio optimization
• ISSN: 1613-6810; 1613-6829
• DOI: 10.1002/smll.202303403

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 Mn2+/4+/Fe2+/3+, Au NPs, and DSCP rapidly. The optimal ratio of Mn/Fe shows excellent H2O2 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 H2O2. Then H2O2 is catalyzed by Mn2+/Fe2+ 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. A pH and glutathione  dual‐responsive cascade nanoreactor is designed and synthesized by adjusting the ratio of Mn/Fe coordinated with syringic acid for targeted delivery of cisplatin prodrugs and biomimetic glucose oxidase to enhance synergistic therapy. The results demonstrate that the full‐featured nanoreactor exhibits intensive chemodynamic therapy effect due to the optimal Mn/Fe ratio to synergistic with chemo‐starvation therapy for anticancer.