Synthesis of doxorubicin-protein conjugates via cobalt coordination chemistry

The use of nanotechnology-based drug delivery systems in the context of cancer treatments has the potential to help target drug chemotherapeutics to tumor cells more precisely while simultaneously reducing off-target toxicity. One of the most prescribed chemotherapeutics, doxorubicin, is an anthracyclines drug that is effective in treating cancer; however, the drug exhibits dose-limiting cardiotoxicity. Dox intercalates DNA, resulting in the deterioration of DNA strands and the ultimate inhibition of DNA and RNA synthesis. Doxorubicin’s chemical structure contains a primary amine group that can be used to crosslink it to a protein. This project focuses on using cobalt coordination chemistry as a novel crosslinking strategy to synthesize conjugates of Dox bound human serum albumin (HSA). The synthesis of conjugates of Dox with HSA will be discussed along with methods for characterization via HPLC that allow the number of Dox molecules bound per protein molecule to be determined.