The development of Metal-Organic Frameworks enclosing ac-tive pharmaceutical ingredients is of considerable interest, as their use in controlled drug release and delivery is very promis-ing. Although nalidixic acid is an antibiotic with a broad spec-trum of biological applications, effective mainly against Gram-negative infections, its oral bioavailability is low due to poor solubility and slow dissolution. Herein, we report new Metal Organic Frameworks (BioMOFs) comprising nalidixic acid and divalent magnesium and manganese ions. These compounds showed adequate cytotoxicity and improved antimicrobial activ-ity, especially against Gram-negative bacteria. These BioMOFS are among the first examples containing active pharmaceutical ingredients as linkers. Importantly, it is shown that a remarka-ble increase of the antimicrobial activity of certain antibiotics may be achieved by delivering them in the form of BioMOFs.

Ovarian cancer is the main cause of death from gynecological cancer, with its poor prognosis mainly related to late diagnosis and chemoresistance (acquired or intrinsic) to conventional alkylating and reactive oxygen species (ROS)-generating drugs. We and others reported that the availability of cysteine and glutathione (GSH) impacts the mechanisms of resistance to carboplatin in ovarian cancer. Different players in cysteine metabolism can be crucial in chemoresistance, such as the cystine/glutamate antiporter system Xc (xCT) and the H₂S-synthesizing enzyme cystathionine β-synthase (CBS) in the pathway of cysteine catabolism. We hypothesized that, by disrupting cysteine metabolic flux, chemoresistance would be reverted. Since the xCT transporter is also able to take up selenium, we used selenium-containing chrysin (SeChry) as a plausible competitive inhibitor of xCT. For that, we tested the effects of SeChry on three different ovarian cancer cell lines (ES2, OVCAR3, and OVCAR8) and in two non-malignant cell lines (HaCaT and HK2). Results showed that, in addition to being highly cytotoxic, SeChry does not affect the uptake of cysteine, although it increases GSH depletion, indicating that SeChry might induce oxidative stress. However, enzymatic assays revealed an inhibitory effect of SeChry toward CBS, thus preventing production of the antioxidant H₂S. Notably, our data showed that SeChry and folate-targeted polyurea dendrimer generation four (SeChry@PURE_G4-FA) nanoparticles increased the specificity for SeChry delivery to ovarian cancer cells, reducing significantly the toxicity against non-malignant cells. Collectively, our data support SeChry@PURE_G4-FA nanoparticles as a targeted strategy to improve ovarian cancer treatment, where GSH depletion and CBS inhibition underlie SeChry cytotoxicity.