Fluorinated Hyaluronic Acid Encapsulated Perfluorocarbon Nanoparticles as Tumor-Targeted Oxygen Carriers to Enhance Radiotherapy.

The efficacy of radiotherapy is significantly constricted by tumor hypoxia. To overcome this obstacle, one promising approach is to use the perfluorocarbon-based O 2 carriers combined with hyperoxic respiration to relieve tumor hypoxia. However, this passively transported oxygen carrier during hyperoxic respiration is prone to cause systemic oxidative stress and toxicity, which further limits its clinical application. Herein, we fabricate O 2 @PFC@FHA NPs for safe and specific oxygen delivery into tumors by using the fluorinated hyaluronic acid to encapsulate O 2 -saturated perfluorocarbon. Due to the interaction between HA and CD44 receptors, more FHA@PFC NPs accumulated in the tumor and the O 2 @PFC@FHA NPs significantly relieved tumor hypoxia. Notably, RT plus O 2 @PFC@FHA NPs resulted in almost threefold therapeutic improvement compared with RT without obvious systemic toxicity. Therefore, the O 2 @FHA@PFC NPs may have great potential to enhance the therapeutic efficacy of radiotherapy in the clinic.