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Enzyme‐Mediated Tumor Starvation and Phototherapy Enhance Mild‐Temperature Photothermal Therapy
Authors:Ge Gao  Yao‐Wen Jiang  Yuxin Guo  Hao‐Ran Jia  Xiaotong Cheng  Yu Deng  Xin‐Wang Yu  Ya‐Xuan Zhu  Hao‐Yue Guo  Wei Sun  Xiaoyang Liu  Jing Zhao  Shihe Yang  Zhi‐Wu Yu  Fatima Maria Sierra Raya  Gaolin Liang  Fu‐Gen Wu
Abstract: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.
Keywords:cancer starvation therapy  enzyme‐enhanced phototherapy  glucose oxidase  mild‐temperature photothermal therapy  thermo‐sensitive liposomes
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