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

Hypoxia is a critical cause of tumor immunosuppression, and it significantly limits the efficacy of many anticancer modalities. Herein, we report an amphiphilic F₁₁-derivative-based oxygen-delivering polyfluorocarbon nanovehicle loading photodynamic DiIC₁₈(5) and reactive oxygen species (ROS)-sensitive prodrug of chemo-immunomodulatory gemcitabine (PF₁₁DG), aimed at relieving tumor hypoxia and boosting antitumor immunity for cancer therapy. We optimized F₁₁-based polyfluorocarbon nanovehicles with a 10-fold enhancement of tumor oxygenation. PF₁₁DG exhibited intriguing capabilities, such as oxygen-dissolving, ROS production, and responsive drug release. In tumors, PF₁₁DG exhibited flexible intratumoral permeation and boosted robust antitumor immune responses upon laser irradiation. Notably, the treatment of PF₁₁DG plus laser irradiation (PF₁₁DG+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.