Yu Qiao, Zhou Jie, Wang Hui, Liu Yong, Zhou Hong, Kang Bin, Chen Hong-Yuan, Xu Jing-Juan
State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing210023, P.R. China.
Key Laboratory of Optic-electric Sensing and Analytical Chemistry for Life Science, Ministry of Education, College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao266042, P.R. China.
Chem Biomed Imaging. 2023 Mar 6;1(3):242-250. doi: 10.1021/cbmi.2c00003. eCollection 2023 Jun 26.
Photothermal therapy (PTT) is hampered by the limited capacity of light penetration, non-specific thermal diffusion damage to surrounding healthy tissues, and thermoresistance originating in heat shock proteins (HSPs). Here, a triple-respondent (triphosphate, glutathione, and pH) cascade nanoreactor was designed through the glucose consumption-induced thermal sensitization strategy. The near-infrared-II (NIR-II) photothermal reagent Bi-Au was encapsulated in a glucose oxidase-based protein-polyphenol structure with the help of the zeolitic imidazolate framework-8 (ZIF-8). The composite nanosystem possesses triple-enzyme activity (glucose oxidase, peroxidase-like, and catalase-like). On one hand, the product of hydrogen peroxide from glycolysis can be converted into reactive oxygen species and oxygen to enhance the chemodynamic therapy and alleviate the state of hypoxia in tumor cells. On the other hand, glucose consumption could down-regulate the expression level of HSPs. The heat resistance ability of cells decreased under starvation and oxidative damage states, which is beneficial to reduce the temperature required for PTT and improve the efficiency of mild PTT. The cascade nanocapsule exhibited high tumor inhibition and proposed a typical synergistic strategy for starvation, chemodynamic, and NIR-II mild photothermal therapy.
光热疗法（PTT）受到光穿透能力有限、对周围健康组织的非特异性热扩散损伤以及热休克蛋白（HSPs）引起的热抗性的限制。在此，通过葡萄糖消耗诱导的热敏化策略设计了一种三响应（三磷酸、谷胱甘肽和pH）级联纳米反应器。近红外二区（NIR-II）光热试剂Bi-Au在沸石咪唑酯骨架-8（ZIF-8）的帮助下被包裹在基于葡萄糖氧化酶的蛋白质-多酚结构中。该复合纳米系统具有三重酶活性（葡萄糖氧化酶、类过氧化物酶和类过氧化氢酶）。一方面，糖酵解产生的过氧化氢产物可转化为活性氧和氧气，以增强化学动力学疗法并缓解肿瘤细胞中的缺氧状态。另一方面，葡萄糖消耗可下调HSPs的表达水平。在饥饿和氧化损伤状态下，细胞的耐热能力降低，这有利于降低PTT所需的温度并提高温和PTT的效率。该级联纳米胶囊表现出高肿瘤抑制作用，并提出了一种典型的饥饿、化学动力学和NIR-II温和光热疗法协同策略。
