Hypoxia is a common characteristic of solid tumors. It is mainly determined by low levels of oxygen resulting
from imperfect vascular networks supplying most tumors. In an attempt to improve the present chemotherapeutic
treatment and reduce associated side effects, several prodrug strategies have been introduced to
achieve hypoxia-specific delivery of cytotoxic anticancer agents. With the advances in nanotechnology, novel delivery
systems activated by the consequent outcomes of hypoxia have been developed. However, developing hypoxia
responsive drug delivery systems (which only depend on low oxygen levels) is currently naïve.
This review discusses four main hypoxia responsive delivery systems: polymeric based drug delivery systems,
oxygen delivery systems combined with radiotherapy and chemotherapy, anaerobic bacteria which are used for delivery
of genes to express anticancer proteins such as tumor necrosis alpha (TNF-α) and hypoxia-inducible transcription
factors 1 alpha (HIF1α) responsive gene delivery systems.