Oxygen-Delivering Polyfluorocarbon Nanovehicles Improve Tumor Oxygenation and Potentiate Photodynamic-Mediated Antitumor Immunity

Hypoxia is a critical cause of tumor immunosuppression, and it significantly limits the efficacy of many anticancer modalities. Herein, we report an amphiphilic F 11 -derivative-based oxygen-delivering polyfluorocarbon nanovehicle loading photodynamic DiIC 18 (5) and reactive oxygen species (ROS)-sensitive prodrug of chemo-immunomodulatory gemcitabine (PF 11 DG), aimed at relieving tumor hypoxia and boosting antitumor immunity for cancer therapy. We optimized F 11 -based polyfluorocarbon nanovehicles with a 10-fold enhancement of tumor oxygenation. PF 11 DG exhibited intriguing capabilities, such as oxygen-dissolving, ROS production, and responsive drug release. In tumors, PF 11 DG exhibited flexible intratumoral permeation and boosted robust antitumor immune responses upon laser irradiation. Notably, the treatment of PF 11 DG plus laser irradiation (PF 11 DG+L) significantly retarded the tumor growth with an 82.96% inhibition in the 4T1 breast cancer model and a 93.6% inhibition in the PANC02 pancreatic cancer model with better therapeutic benefits than non-oxygen-delivering nanovehicles. Therefore, this study presents an encouraging polyfluorocarbon nanovehicle with deep tumor-penetrating and hypoxia-relieving capacity to boost antitumor immunity for cancer treatment.