Glucose oxidase (GOx)-mediated starvation circumvents the energy supply for tumor growth, which has been proved as a potent tumor treatment modality. However, tumor hypoxia negatively affects the efficacy of oxygen-involved glucose decomposition reaction. Moreover, curative effect via glucose depletion is not usually satisfactory enough and adjuvant remedies are always required for a promoted tumor ablation. Herein, a multifunctional nanoreactor based on hollow Bi2Se3 nanoparticles was developed by loading oxygenated perfluorocarbon (PFC) and surface modification with GOx, which was exploited for an enhanced tumor starvation and highly sensitive photothermal therapy (PTT). GOx-mediated tumor starvation could impede the adenosine triphosphate (ATP) generation and further downregulate the expression of heat shock protein (HSP) to decrease the thermoresistance of cells. Afterwards, near infrared (NIR) laser irradiation was performed not only to trigger sensitized PTT but also to initiate the release of encapsulated oxygen to relieve local hypoxia. Then, such GOx-mediated tumor starvation would be further amplified, accompanying with secondary enhanced suppression of HSP. Both in vitro and in vivo investigations demonstrated that such nanoreactor can realize a fascinating therapeutic outcome with minimal adverse effects in virtue of the improved synergistic starvation therapy and PTT. Taken together, the proposed treatment paradigm may inspire the future development of more intelligent nanoplatforms toward high efficient cancer therapy.

中文翻译：

---

在近红外（NIR）窗口中进行光活化氧气自给的饥饿疗法，并以更高的敏感性提高辅助热疗诱导的肿瘤消融。

葡萄糖氧化酶（GOx）介导的饥饿避免了肿瘤生长的能量供应，这已被证明是有效的肿瘤治疗方法。然而，肿瘤缺氧负面影响氧参与的葡萄糖分解反应的功效。此外，通过葡萄糖耗竭的治疗效果通常不能令人满意，并且对于促进肿瘤消融总是需要辅助疗法。本文中，通过负载氧化的全氟化碳（PFC）和用GOx进行表面修饰，开发了基于中空Bi2Se3纳米粒子的多功能纳米反应器，该纳米反应器被用于增强肿瘤饥饿和高度敏感的光热疗法（PTT）。GOx介导的肿瘤饥饿可能会阻碍三磷酸腺苷（ATP）的生成，并进一步下调热休克蛋白（HSP）的表达，从而降低细胞的耐热性。之后，执行近红外（NIR）激光照射不仅触发致敏的PTT，而且开始释放封装的氧气以缓解局部缺氧。然后，这种GOx介导的肿瘤饥饿将被进一步放大，伴随着对HSP的继发性增强抑制。体外和体内研究均表明，由于改进的协同饥饿疗法和PTT，这种纳米反应器可以实现令人着迷的治疗结果，且不良反应最小。在一起