Fluorene methoxycarbonyl-PEG-deferoxamine conjugates "hitchhike" with albumin in situ for iron overload therapy

Abstract

Although deferoxamine (DFO) has been approved for the treatment the iron overloaded diseases, its clinical application is impeded by very short circulation time and its relating toxicity. In this work, the fluorene methoxycarbonyl (FMOC) for "albumin hitchhiking" was used to prolong the plasma circulation time of DFO and reduce toxicity. The designed FMOC-PEG-DFO conjugates were found to reversible bind to albumin and gradually release DFO in vivo. Herein, the FMOC-PEG₁₀₀₀-DFO conjugates could increase 30 times the blood circulation time of DFO with the improvement of the iron elimination efficacy. Meanwhile, the conjugates markedly reduced the cytotoxicity of DFO. Taken together, the result demonstrated the FMOC-PEG₁₀₀₀-DFO conjugates could be a potential therapeutic choice for iron-overload-related diseases.

Keywords: Albumin; Conjugates; Deferoxamine; Half-life; Iron overload.