Dual-responsive manganese-based metal–organic framework coated with aptamer-tagged macrophage membrane: an innovative approach for enhanced chemodynamic therapy and MR imaging

Abstract Manganese-based metal–organic frameworks (Mn MOFs) represent a highly promising class of materials, characterized by their low toxicity, oxidative capabilities, and biocompatibility, which render them particularly advantageous for various biomedical applications. This study presents the development of a biodegradable, intelligent carrier utilizing MOFs with Mn center and 4,4'-dithiobisbenzoic acid ligands that responds to pH changes and glutathione levels for targeted chemodynamic therapy. The synthesized nanoparticles demonstrated remarkable encapsulation efficiency and a doxorubicin hydrochloride (DOX) loading capacity of 84.95 ± 1.7%. To improve biocompatibility, the DOX-loaded manganese metal–organic frameworks (Mn MOFs) were encapsulated with macrophage cells (RAW 264.7) membranes (MCM). The Sgc8-c DNA aptamer, known for its specific targeting of the PTK7 receptor, was integrated into the formulation to develop the Apt–Mn MOF–DOX–MCM. In vitro studies indicated that the Mn MOFs degrade into Mn2+ ions under acidic and high glutathione conditions, promoting DOX release and initiating a Fenton-like reaction to improve therapeutic efficacy. The Apt–Mn MOF–DOX–MCM formulation exhibited increased cytotoxicity, enhanced cellular uptake, and efficiently inhibited colony formation in PTK7-overexpressing B16F0 cancer cells. Preclinical studies revealed that this targeted system significantly reduced tumor size in B16F0 tumor-bearing C57BL/6 mice compared to non-targeted formulations. Furthermore, both Apt–Mn MOF–DOX–MCM and Mn MOF–DOX–MCM showed potential as MRI contrast agents, with favorable accumulation at tumor sites. In conclusion, the developed platform represents a promising theranostic approach, integrating diagnostic imaging with targeted drug delivery for improved cancer treatment.