Ren Junjie, Zhang Lei, Zhang Jiayi, Zhang Wei, Cao Yang, Xu Zhigang, Cui Hongjuan, Kang Yuejun, Xue Peng
Key Laboratory of Luminescent and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, School of Materials and Energy, Southwest University, Chongqing, 400715, China; Chongqing Engineering Research Center for Micro-Nano Biomedical Materials and Devices, Southwest University, Chongqing, 400715, China.
Institute of Sericulture and System Biology, Southwest University, Chongqing, 400716, China.
Biomaterials. 2020 Mar;234:119771. doi: 10.1016/j.biomaterials.2020.119771. Epub 2020 Jan 9.
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 BiSe 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.
葡萄糖氧化酶（GOx）介导的饥饿疗法可阻断肿瘤生长的能量供应，这已被证明是一种有效的肿瘤治疗方式。然而，肿瘤缺氧会对涉及氧气的葡萄糖分解反应的疗效产生负面影响。此外，通过消耗葡萄糖实现的治疗效果通常不够理想，往往需要辅助治疗来促进肿瘤消融。在此，通过负载含氧全氟碳（PFC）并进行GOx表面修饰，开发了一种基于中空BiSe纳米颗粒的多功能纳米反应器，用于增强肿瘤饥饿疗法和高灵敏度光热疗法（PTT）。GOx介导的肿瘤饥饿可阻碍三磷酸腺苷（ATP）的生成，并进一步下调热休克蛋白（HSP）的表达，从而降低细胞的热抗性。随后，进行近红外（NIR）激光照射，不仅可触发敏化光热疗法，还可引发封装氧气的释放，以缓解局部缺氧。然后，这种GOx介导的肿瘤饥饿将进一步增强，同时伴随对HSP的二次增强抑制。体外和体内研究均表明，这种纳米反应器凭借改进的协同饥饿疗法和光热疗法，可实现极具吸引力的治疗效果，且副作用极小。综上所述，所提出的治疗模式可能会激发未来开发更智能的纳米平台用于高效癌症治疗。
