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.

中文翻译：

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输送氧气的多氟化碳纳米汽车改善了肿瘤的氧合作用并增强了光动力介导的抗肿瘤免疫力

缺氧是肿瘤免疫抑制的关键原因，它严重限制了许多抗癌方法的功效。在此，我们报道了一种两亲性的基于F ₁₁的输氧多氟化碳纳米载体，其载有化学免疫调节吉西他滨（PF ₁₁ DG）的光动力学DiIC ₁₈（5）和活性氧（ROS）敏感型前药，旨在缓解肿瘤缺氧并提高抗癌免疫力。我们优化了基于F ₁₁的聚碳纳米汽车，使肿瘤氧合提高了10倍。PF ₁₁ DG表现出令人着迷的功能，例如溶解氧，ROS产生和响应性药物释放。在肿瘤中，PF ₁₁DG在激光照射下表现出柔性的肿瘤内渗透并增强了强大的抗肿瘤免疫反应。值得注意的是，PF ₁₁ DG加上激光照射（PF ₁₁ DG + L）的治疗显着延迟了肿瘤的生长，在4T1乳腺癌模型中抑制率为82.96％，在PANC02胰腺癌模型中抑制率为93.6％，其治疗效果优于无氧输送纳米车辆。因此，本研究提出了令人鼓舞的具有深度的肿瘤渗透性和缺氧缓解能力的多氟化碳纳米载体，以增强抗肿瘤免疫力。