A Mesoporous Gd-MOF with Lewis Basic Sites for 5-Fu Delivery and Inhibition of Human Lung Cancer Cells In Vivo and In Vitro

Abstract

A hydrolytically stable mesoporous Gd(III)-MOF {[Gd2(TATAB)2]·6 DMF}n (1) has been successfully prepared by reaction of Gd(NO3)3·6H2O with a flexible ligand 4,4′,4′′-s-triazine-1,3,5-triyltri-p-aminobenzoate (H3TATAB) under solvothermal conditions. Further, the nanostructure 1 could be obtained via an ultrasonic treatment method. Nitrogen adsorption measurements revealed the presence of mesoporosity as well as a moderate high BET surface areas in the activated nanostructure 1 (1a), which was further used in the 5-Fu loading with the uptake capacity of 47 wt%. Meanwhile, the controlled release of 5-Fu in a simulated human body with liquid phosphate-buffered saline solution was realized. In the biological study, the anti-proliferation activity of 5-Fu@1a on A549 human non-small lung cancer (NSCLC) cells after 5-Fu@1a exposure was evaluated by the CCK-8 preformation. The effect of 5-Fu@1a on A549 NSCLC cell migration and invasion ability was detected by transwell assay. The mechanism was revealed by the detection of the NLRP3 inflammasome activation level in A549 through western blot and ELISA assay. For further explore the inhibitory effect of 5-Fu@1a, the anti-tumor ability was evaluated in the in vivo xenograft model.