Current developments in nanotechnology for improved cancer treatment, focusing on tumor hypoxia

Hypoxia is a common feature of the tumor microenvironment, which is characterized by tissue oxygen deficiency due to an aggressive proliferation of cancer cells. Hypoxia activates hypoxia-inducible factor-dependent signaling, which in turn regulates metabolic reprogramming, immune suppression, resistance to apoptosis, angiogenesis, metastasis, and invasion to secondary sites. In this review, we provide an overview of the use of nanotechnology to harmonize intra-tumoral oxygen or suppress hypoxia-related signaling for an improved efficacy of cancer treatment. The biological background was followed by conducting a literature review on the (1) nanoparticles responsible for enhancing oxygen levels within the tumor, (2) nanoparticles sensitizing hypoxia, (3) nanoparticles suppressing hypoxia-inducing factor, (4) nanoparticles that relieve tumor hypoxia for enhancement of chemotherapy, photodynamic therapy, and immunotherapy, either individually or in combination. Lastly, the heterogeneity of cancer and limitations of nanotechnology are discussed to facilitate translational therapeutic treatment.