低氧状态可能增强癌细胞对化疗药物的耐药性并严重削弱化疗的有效性。为减轻或逆转低氧状态，许多努力已经在引入更多氧气到肿瘤微环境（TME）方面展开。与此截然相反，在本研究中，设计了一种新型纳米载体来进一步耗尽低氧TME中的氧气水平。通过创建这样一个氧耗尽的TME，低氧选择性细胞毒素可以有效发挥作用，并实现氧耗尽引发的化疗。因此，在本文中，采用引发低氧状态的药物交替吡お兹（TPZ）与食药监发行许可的全氟碳化物（PFC）和光敏剂吲哚菁绿（ICG）共同纳入聚（乳酸-糖酸）（PLGA）纳米乳液（ICG/TPZ@PPs）以治疗低氧肿瘤。通过物理溶解和肿瘤照射后的光动力学耗尽，可增强低氧化疗的激活效果，改善多重治疗的协同作用。当达到局部肿瘤富集后，PFC介导的氧溶解与进一步的ICG介导的近红外（NIR）激光照射下的光动力疗法（PDT）能够诱发增强的低氧状态，从而激活核载杂交了TPZ的抗肿瘤活性，以增强细胞毒性共同作用。值得注意的是，体内实验结果显示，缺氧的ICG/TPZ@PPs基于光热疗法（PTT），PDT和低氧激活化疗具有卓越的肿瘤消融协同作用而没有明显的副作用，因此，纳米载体的广泛应用前景可预期。

Hypoxia may enhance the chemoresistance of cancer cells and can significantly compromise the effectiveness of chemotherapy. Many efforts have been made to relieve or reverse hypoxia by introducing more oxygen into the tumor microenvironment (TME). Acting in a diametrically opposite way, in the current study, a novel nanocarrier was designed to further exhaust the oxygen level of the hypoxic TME. By creating such an oxygen depleted TME, the hypoxia-selective cytotoxin can work effectively, and oxygen exhaustion triggered chemotherapy can be achieved. Herein, deoxygenation agent, FDA-approved perfluorocarbon (PFC) and photosensitizer indocyanine green (ICG) for oxygen depletion, along with the hypoxia-activating drug tirapazamine (TPZ), were coincorporated within the poly(lactic-co-glycolic acid) (PLGA) nanoemulsion (ICG/TPZ@PPs) for the treatment of hypoxic tumors. Following hypoxia amplifying through physical oxygen dissolution and photodynamic depletion in tumors, hypoxic chemotherapy could be effectively activated to improve multitreatment synergy. After achieving local tumor enrichment, PFC-mediated oxygen dissolution combined with further ICG-mediated photodynamic therapy (PDT) under near-infrared (NIR) laser irradiation could induce enhanced hypoxia, which would activate the antitumor activity of codelivered TPZ to synergize cytotoxicity. Remarkably, in vivo experimental results exhibited that deoxygenated ICG/TPZ@PPs-based photothermal therapy (PTT), PDT, and hypoxia activated chemotherapy have an excellent synergistic ablation of tumors without obvious side effects, and therefore, a broad prospect of application of this nanocarrier could be expected.