The research of how cells sense and adapt the oxygen deficiency has been recognized as worth winning a Nobel Prize in 2019. Understanding hypoxia-driven molecular machinery paved a path for novel strategies in fighting hypoxia-related diseases including cancer. The oxygen depletion inside the tumor provokes HIF-1 dependent gene and protein expression which helps the tumor to survive. For this reason, tumor related molecules are in the spotlight for scientists developing anticancer agents. One such target is carbonic anhydrase IX (CA IX)-a protein located on the outer cell membrane of most hypoxic tumor cells. This offers the opportunity to exploit it as a target for delivery of cytotoxic drugs, dyes, or radioisotopes to cancer cells. Therefore, researchers investigate CA IX specific small molecules and antibodies as tumor-targeting moieties in nanosystems and conjugates which are expected to overcome the limitations of some existing diagnostic and treatment strategies. This review covers the vast majority of CA IX-targeted systems (nanoparticle and conjugate based) for both therapeutic and imaging purposes published up to now. Furthermore, it shows their stage of development and gives an assessment of their clinical translation possibilities.
Keywords: carbonic anhydrase IX; drug delivery; small molecule and antibody−drug conjugates; targeted nanosystems; tumor targeting.