Figure 4.

Schematic of the formation of a hypoxic environment and the potential targeting of this microenvironment with HAPs. RBCs transport oxygen through the blood vasculature, and hypoxia forms when this diffusion-limited process delivers insufficient oxygen to cells distant to the vasculature (blue cells). The extreme case of anoxia (grey cells) regularly results in necrotic cell death. HAPs take advantage of the hypoxic environment of tumours to deliver cytotoxic compounds to these tumour regions, where the prodrug is either enzymatically cleaved by the cells metabolic machinery or undergoes a conformational change in response to the low oxygen partial pressure. HAPs, hypoxia-activated prodrugs; RBCs, red blood cells.