Targeted delivery of drugs to specific regions or cells in the body is a method used to localize, prolong, and have a protective interaction between a drug and the tissue. In our lab we seek to use hemoglobin as a mediator for active targeted drug delivery to monocytes and macrophages. Through this method, off target side effects can be reduced and a more uniform effect of the drug can be established.
Hemoglobin (Hb) in blood is naturally scavenged by macrophages and monocytes through the CD-163 mediated endocytosis pathway. In the blood stream, Hb rapidly dissociates into dimers. These dimers can then irreversibly bind to the protein haptoglobin (Hp). The Hp-Hb complex can then dock at the CD-163 receptor and trigger endocytosis. The Hb-Hp complex will then be taken up by the macrophages and subsequently degraded by lysozomal enzymes. A diagram of this pathway can be seen in the figure below.
Through the work in our lab we have demonstrated hemoglobin based drug delivery methods can successfully deliver drugs to macrophages and monocytes. This work has shown that various therapeutics including anticancer therapeutics such as dicloroacetic acid and liposomes.
- N. Zhang and A. F. Palmer, “Development of a dichloroacetic acid-hemoglobin conjugate as a potential targeted anti-cancer therapeutic,” Biotechnology and Bioengineering 108: 1413-1420 (2011)
- N. Zhang and A. F. Palmer, “Liposomes surface conjugated with human hemoglobin target delivery to macrophages,” Biotechnology & Bioengineering 109: 823-9 (2012)