Fabrication of marizomib-loaded zeolitic imidazolate framework-8@manganese dioxide for promising drug delivery system of glioma cancer cells

Abstract

Marizomib is a novel, irreversible, brain-penetrant pan-proteasome inhibitor with encouraging findings in preclinical models and early-stage clinical trials for patients with newly diagnosed and recurrent glioblastoma. Marizomib (MRZ)-loaded zeolitic imidazolate framework-8 (ZIF-8) and manganese dioxide (MnO2) (termed as MRZ-ZIF-8 @MnO2) nanoparticles, a smart-functional therapeutic system, were prepared for the treatment of glioma cancer. Fourier transforms infrared (FTIR) and transmission electron microscope (TEM) were used to assess the structural and morphology properties of drug-loaded ZIF-8-NPs. The findings demonstrated this drug delivery carrier's narrow and particle size distribution. The anticancer drug MRZ released from the NPs was measured. The cell viability of glioma cancer cells (C6 and U87) treated with NPs was established using the cell counting kit-8. The in vitro proliferation of drug-loaded ZIF-8-NPs was substantially increased than that of free MRZ and drug-loaded ZIF-8-NPs treated cells. In addition, The C6 and U87 cell morphological staining studies, such as dual staining (acridine orange/ethidium bromide, AO/EB) and nuclear staining (4′,6-diamidino-2-phenylindole, DAPI), ascertain that the drug-loaded ZIF-8-NPs stimulates the apoptosis in glioma cancer cell lines. The results of morphological changes show that a high apoptosis level was found with drug-loaded ZIF-8-NPs. Reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) validate the apoptotic mode of cancer cell death via the MMP pathway. These findings suggest that the as-fabricated MRZ-ZIF-8 @MnO2-NPs with the synergetic anticancer drug might be applied to treat glioma cancer.