Enzyme-Mediated Tumor Starvation and Phototherapy Enhance Mild-Temperature Photothermal Therapy
Enzyme-Mediated Tumor Starvation and Phototherapy Enhance Mild-Temperature Photothermal Therapy
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DOI：
10.1002/adfm.201909391
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发表时间：
2020-02-26
影响因子：
19
通讯作者：
Wu, Fu-Gen
中科院分区：
文献类型：
--
作者：
Gao, Ge;Jiang, Yao-Wen;Wu, Fu-Gen
与传统的肿瘤光热治疗(PTT)相比，亚温PTT对正常组织的损伤较小，但由于过表达的热休克蛋白(HSP)而引入肿瘤耐热性。亚温PTT期间大剂量的HSP抑制剂可能会导致毒副作用。葡萄糖氧化酶(GOx)消耗葡萄糖，导致三磷酸腺苷供应受限，进而抑制热休克蛋白。因此，HSP抑制剂和GOX的联合使用不仅可以提高温和的PTT，而且还可以将该抑制剂的毒性降至最低。然而，用于提高其低温肿瘤PTT效率的GOX和HSP抑制剂包裹的纳米结构尚未见报道。温敏型GOX/吲哚青绿/赤霉酸(GA)脂质体(GOIGL)通过释放的GA和GOX协同抑制肿瘤HSP，以及另一种酶增强的光疗效应，提高了肿瘤的亚温PTT效率。体外和体内结果表明，这种肿瘤饥饿和光疗的策略显着提高了亚温肿瘤PTT的效率。这一策略可以激励人们设计更精致的平台，将温和的PTT与其他治疗方法相结合，以实现更有效的癌症治疗。
Compared with conventional tumor photothermal therapy (PTT), mild-temperature PTT brings less damage to normal tissues, but also tumor thermoresistance, introduced by the overexpressed heat shock protein (HSP). A high dose of HSP inhibitor during mild-temperature PTT might lead to toxic side effects. Glucose oxidase (GOx) consumes glucose, leading to adenosine triphosphate supply restriction and consequent HSP inhibition. Therefore, a combinational use of an HSP inhibitor and GOx not only enhances mild-temperature PTT but also minimizes the toxicity of the inhibitor. However, a GOx and HSP inhibitor-encapsulating nanostructure, designed for enhancing its mild-temperature tumor PTT efficiency, has not been reported. Thermosensitive GOx/indocyanine green/gambogic acid (GA) liposomes (GOIGLs) are reported to enhance the efficiency of mild-temperature PTT of tumors via synergistic inhibition of tumor HSP by the released GA and GOx, together with another enzyme-enhanced phototherapy effect. In vitro and in vivo results indicate that this strategy of tumor starvation and phototherapy significantly enhances mild-temperature tumor PTT efficiency. This strategy could inspire people to design more delicate platforms combining mild-temperature PTT with other therapeutic methods for more efficient cancer treatment.