Title:

Glutathione-Sensitive Nanocarrier Covalent Organic Frameworks for the Synergistic Release of Chemotherapeutics

Metal Organic Frameworks, known as MOFs are porous, crystalline structures that are made up of metal centers bonded to organic linkers. Depending on the metal ion and linker, the size of the pores and geometry of the molecule can vary greatly. These pores can absorb and encapsulate other molecules, depending on both the size of the molecule and the pores, as well as potential intermolecular interactions between the molecule and framework. By changing the linkers, you can also alter the functionality of the MOF. This project uses a Zn-based MOF as a nanocarrier for chemotherapeutics, specifically doxorubicin and 5-fluorouracil. Using this MOF is important because of its ability to selectively transport the cancer drug to malignant cells, which will limit side effects that are often associated with these medications. The reason this is possible is because of the dithiol present in our organic linker. Glutathione is a peptide found in the body in all cells, but much more prominently in cancer cells, with a concentration up to 1000x higher than in healthy cells. This peptide breaks down S-S bonds in the body, so it will also break down our MOF, releasing the drug into the cell. The hope is that because of the higher concentration of glutathione in cancer cells, the MOF will go to these cells selectively and break down and release the medication in primarily the sick cells and not the healthy cells. This will lower overall side effects because the healthy cells would be less effected by the medication.

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