Synthesis of doxorubicin-ablumin conjugates via cobalt coordination chemistry: The effect of reaction conditions on overall protein stability

Polymer-drug conjugates have become a common tool in therapeutics to reduce the chances of pharmacotoxicity, often seen in patients undergoing chemotherapy, and to enhance targeted drug delivery. The demand for more novel forms of drug delivery has increased the efforts to develop new drug designs. Our research utilizes cobalt coordination chemistry for the synthesis of protein-drug conjugates. More specifically, this researched was aimed at crosslinking human serum albumin (HSA) and Doxorubicin via cobalt coordination chemistry. In a reversible reaction, cobalt can be used to crosslink amine-containing molecules; such as the primary amine contained in Doxorubicin and the lysine residue of HSA, via coordinate covalent bonding. The ultimate goal of this research endeavor is to alter the biodistribution of Dox in vivo to reduce the systemic toxicity of the drug, which displays dose limiting cardiotoxicity. The use of high- performance liquid chromatography (HPLC) and dynamic light scattering (DLS) were used in identifying optimal reaction conditions for the synthesis of an HAS-Dox conjugate