Biocompatible, Crystalline, and Amorphous Bismuth-Based Metal–Organic Frameworks for Drug Delivery

The synthetic flexibility of metal-organic frameworks (MOFs) with high loading capacities and biocompatibility makes them ideal candidates as drug delivery systems (DDSs). Here, we report the use of CAU-7, a biocompatible bismuth-based MOF, for the delivery of two cancer drugs, sodium dichloroacetate (DCA) and α-cyano-4-hydroxycinnamic acid (α-CHC). We achieved loadings of 33 and 9 wt % for DCA and α-CHC, respectively. Interestingly, CAU-7 showed a gradual release of the drugs, achieving a release time of up to 17 days for DCA and 31 days for α-CHC. We then performed mechanical and thermal amorphization processes to attempt to delay the delivery of guest molecules even more. With the thermal treatment, we were able to achieve an outstanding 32% slower release of α-CHC from the thermally treated CAU-7. Using in vitro studies and endocytosis inhibitors, confocal microscopy, and fluorescence-activated cell sorting, we also demonstrated that CAU-7 was successfully internalized by cancer cells, partially avoiding lysosome degradation. Finally, we showed that CAU-7 loaded either with DCA or α-CHC had a higher therapeutic efficiency compared with the free drug approach, making CAU-7 a great option for biomedical application.