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 MIL-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 MIL-88B(Fe)@ZIF-8 was then used as a drug/cargo delivery vehicle for loading doxorubicin (DOX), manganese oxide (MnO) nanoparticles, and folic acid (FA), forming a multifunctional nanoplatform (denoted M@ZMDF). Importantly, the resulting M@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 Fe in the tumor microenvironment. Consequently, DOX played dual roles as a chemotherapeutic drug and a fluorescent imaging agent. Also, the released Fe could mediate the Fenton reaction and intracellularly generate toxic hydroxyl radicals in the presence of high glutathione in cancer cells. In addition, MnO nanoparticles could participate in magnetic resonance imaging. Therefore, the versatile M@ZMDF nanoplatforms have great potential for smart cancer therapy.