Fabrication of Versatile Hollow Metal-Organic Framework Nanoplatforms for Folate-Targeted and Combined Cancer Imaging and Therapy

Metal-organic frameworks (MOFs) have received extensive attention in the field of biomedicine, particularly serving as multifunctional theranostic nanoplatforms by integrating chemodrugs, imaging agents, and targeting agents. Herein, we report a facile strategy for the fabrication of a hollow and monodisperse MOF (denoted hMIL-88B(Fe)@ZIF-8) consisting of ZIF-8 nanoparticles loaded on the external shell of hollow MIL-88B(Fe). In particular, the hybrid hollow MOF was constructed by partially etching spindlelike MIL-88B(Fe) nanoparticles with 2-methylimidazole in the presence of zinc ions. The obtained hMIL-88B(Fe)@ZIF-8 was then used as a drug/cargo delivery vehicle for loading doxorubicin (DOX), manganese oxide (MnOx) nanoparticles, and folic acid (FA), forming a multifunctional nanoplatform (denoted hM@ZMDF). Importantly, the resulting hM@ZMDF exhibited a specific targeting property for the FA receptor-overexpressed cancer cells (MCF-7 and HepG-2 cells) and then it unloaded DOX and Fe3+ in the tumor microenvironment. Consequently, DOX played dual roles as a chemotherapeutic drug and a fluorescent imaging agent. Also, the released Fe3+ could mediate the Fenton reaction and intracellularly generate toxic hydroxyl radicals in the presence of high glutathione in cancer cells. In addition, MnOx nanoparticles could participate in magnetic resonance imaging. Therefore, the versatile hM@ZMDF nanoplatforms have great potential for smart cancer therapy.