Drug Delivery to Hypoxic Tumors Targeting Carbonic Anhydrase IX

Hypoxia is a feature of many solid tumors that induces the upregulation of various proteins favoring tumor cell survival and progression. It contributes significantly to resistance to chemotherapy and radiotherapy, raising the demand for novel approaches to enhance the delivery of chemotherapeutic drugs to hypoxic tumor environments. In this chapter, we discuss the role of hypoxia in cancer, along with its massive implications for tumor biology. Several epitopes have been identified as being overexpressed under hypoxic conditions compared to normal tissues and therefore can serve as compelling therapeutic targets and potential biomarkers for enhancing the detection of solid tumors, as well as the efficacy of chemotherapy under hypoxia. Among these epitopes, one of the most promising is carbonic anhydrase IX. We present herein recent developments in drug delivery strategies targeting carbonic anhydrase IX for tumor detection, treatment, or both (theranostic systems). Within this focus, we also describe strategies that overcome cancer cell resistance and help improve the retention of chemotherapeutic drugs in the hypoxic tumor microenvironment.