Hypoxia-activated nanomedicines for effective cancer therapy.

Hypoxia, a common characteristic in solid tumors, is found in phenotypically aggressive cancers that display resistance to typical cancer interventions. Due to its important role in tumor progression, tumor hypoxia has been considered as a primary target for cancer diagnosis and treatment. An advantage of hypoxia-activated nanomedicines is that they are inactive in normoxic cells. In hypoxic tumor tissues and cells, these nanomedicines undergo reduction by activated enzymes (usually through 1 or 2 electron oxidoreductases) to produce cytotoxic substances. In this review, we will focus on approaches to design nanomedicines that take advantage of tumor hypoxia. These approaches include: i) inhibitors of hypoxia-associated signaling pathways; ii) prodrugs activated by hypoxia; iii) nanocarriers responsive to hypoxia, and iv) bacteria mediated hypoxia targeting therapy. These strategies have guided and will continue to guide nanoparticle design in the near future. These strategies have the potential to overcome tumor heterogeneity to improve the efficiency of radiotherapy, chemotherapy and diagnosis.