This work focuses on conjugating the anti-cancer drug dichloroacetic acid (DCA) to the monocyte/macrophage targeting protein hemoglobin (Hb). The DCA–Hb conjugate carries approximately 12 DCA molecules per Hb tetramer, and binds to haptoglobin (Hp) forming stable DCA–Hb–Hp complexes, in a similar manner to unmodified Hb. The results of this study show that DCA–Hb–Hp is taken up by the monocytic cancer cell line THP-1, where it depolarizes the mitochondrial membrane potential, thereby inhibiting cancerous cell growth at a comparable level to free DCA. Taken together, the results of this study show promise for the use of the DCA–Hb conjugate as a potential therapeutic to treat monocytic leukemia. Biotechnol. Bioeng. 2011; 108:1413–1420. © 2011 Wiley Periodicals, Inc.
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