Alleviating tumor hypoxia with perfluorocarbon-based oxygen carriers

Hypoxia is a major impediment to many foremost cancer treatments that require O2 for generation of tumoricidal reactive oxygen species. Liquid perfluorocarbons (PFCs) are inert gas solvents that help alleviate this oxygen deficit situation. PFC nanoemulsions have demonstrated oxygen delivery to tissues. The lifetime of 1O2 in PFCs is considerably expanded. PFC nanodroplets extravasate and accumulate in tumors. Alternatively, PFCs stabilize injectable O2 microbubbles. On-demand local O2 delivery is facilitated by ultrasound. Liquid PFC nanodroplets that convert into microbubbles upon activation provide another shuttle for O2-delivery. PFC nanocarriers can also be enriched with fluorescent dyes, radiopaque materials, photo(sono)sensitizers, loaded with chemotherapeutics, and fitted with targeting devices, or stimuli-responsive functions for image-guided theranostics. We review recent literature on PFC-based O2 carriers to enhance the efficacy of radiotherapy, photo(sono)dynamic therapy and chemotherapy. Of particular relevance to this series of reviews, PFC-based carriers may provide novel strategies to promote T-cell trafficking into tumors to improve immune responses.