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Tumor cells obtain energy supply from different metabolic pathways to maintain survival. In this study, a tumor acidity-responsive spherical nanoparticle (called as LMGC) was designed by attaching glucose oxidase (GOx) and mineralizing calcium carbonate on the surface of liquid metal nanoparticles to integrate the synergistic effect of adenosine triphosphate (ATP) generation inhibition and photothermal therapy (PTT) for enhanced tumor therapy. After GOx catalysis, the process of glycolysis was inhibited, and the increased H 2 O 2 level enhanced the intratumoral oxidative stress. Besides, the gluconic acid production accelerated the degradation of LMGC and promoted Ca2+-mediated mitochondrial dysfunction. The inhibition of glycolysis and mitochondrial metabolism could significantly reduce ATP production and down-regulate heat shock protein (HSP) expression, which would reduce tumor cells heat resistance and improve PTT therapeutic effect. This liquid metal-based ATP inhibition system with enhanced therapeutic effect will find great potential for tumor treatment. [ABSTRACT FROM AUTHOR]

Advances in enzymes involve an efficient biocatalytic process, which has demonstrated great potential in biomedical applications. However, designing a functional carrier for enzymes equipped with satisfactory degradability and loading efficiency, remains a challenge. Here, based on transformable liquid metal (LM), a spinose nanodrum is designed as protein carrier to deliver enzyme for tumor treatment. With the assistance of spines and a special drum‐like shape, it is found that the spiny LM can carry much more enzymes than spherical LM under the same condition. Benefiting from the satisfactory enzyme loading efficiency of spiny LM, a plasma amine oxidase immobilized spinose LM nanosystem enveloped with epigallocatechin gallate (EGCG)‐Fe3+ (LMPE) is fabricated for photothermal and cascade catalytic tumor therapy. Activated by the acidic condition in the tumor microenvironment, the LMPE can oxidize spermine (Spm) and spermidine (Spd) to generate hydrogen peroxide (H2O2) for Fenton catalytic reaction to produce the lethal hydroxyl radical (•OH) for tumor cell killing. Combined with remarkable photothermal performance of LM, LMPE exhibits significant inhibition of tumor in vivo. [ABSTRACT FROM AUTHOR]

The clinical application of antitumor immunotherapy still faces severe challenges related to efficacy. Here, a light‐triggered core–shell nanosystem is designed to boost antitumor immune response via controlled release of anti‐PD‐L1 (αPD‐L1) antibodies and enhanced antigen presentation. The nanosystem (AZ‐P@P) is constructed via integrating gold nanorods (AuNRs) as a photothermal core and zeolitic imidazolate framework‐8 (ZIF‐8) as a shell for aPD‐L1 delivery, and further PEGylating. In the nanosystem, the ZIF‐8 shell protects αPD‐L1 antibody from the complex physiological environment and hyperthermia. Once accumulated at the tumor site, AZ‐P@P under near‐infrared (NIR) light‐triggered heating induces tumor cell deaths releasing tumor‐derived protein antigens (TDPAs) and adenosine triphosphate (ATP). Thereafter, the released ATP degrades the ZIF‐8 shell to expose the AuNRs, which can promote intratumoral T cell infiltration by capturing TDPAs and transporting them to dendritic cells (DCs). Concurrently, a large amount of αPD‐L1 is released in situ to reinvigorate T cell activity. Mechanistic studies reveal that AZ‐P@P promotes the maturation of DCs and the infiltration of activated T cells, thus eliciting a robust antitumor immunity. It is demonstrated that AZ‐P@P triggered by NIR light can significantly destroy primary tumors and suppress metastasis. This multiple immunoregulatory system provides a promising tool for tumor treatment. [ABSTRACT FROM AUTHOR]