Traditional chemotherapeutics continue to induce toxic effects in healthy, non-cancerous cells. Better targeting of such therapies to only the diseased cells remains an ambitious goal. The use of nanotechnology in designing better treatments holds great promise in lessening the burden of chemotherapy on patients while simultaneously producing an increased therapeutic effect. Researchers at TWU are exploring the use of nanotechnology to target and kill cancer cells. Specifically, protein-drug conjugates are being explored. Here we report the synthesis of an albumin-doxorubicin (dox) conjugate based on our cobalt crosslinking strategy. The chemistry utilized relies on the stability/lability of cobalt based on its oxidation state to facilitate release of therapeutic only under reducing conditions. Cobalt was used to crosslink the amine functional group in dox to lysine residues on albumin. The dox-albumin conjugate was stable under oxidative conditions but released bound dox under reducing conditions (1-10 mM reduced glutathione). Details of the conjugation efficiency and release of dox under reducing conditions will be discussed.

Synthesis of an albumin-doxorubicin prodrug conjugate via a traceless, reductively labile cobalt crosslinking strategy

2019 Spring National Meeting

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