Enzyme-Mediated Tumor Starvation and Phototherapy Enhance Mild-Temperature Photothermal Therapy

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.