Biomineralized Two‐Enzyme Nanoparticles Regulate Tumor Glycometabolism Inducing Tumor Cell Pyroptosis and Robust Antitumor Immunotherapy

Zhang, Sijia; Zhang, Ying; Feng, Yong; Wu, Jiayan; Hu, Yingying; Lin, Lin; Xu, Caina; Chen, Jie; Tang, Zhaohui; Tian, Huayu; Chen, Xuesi

doi:10.1002/adma.202206851

Cited by 90 publications

(51 citation statements)

References 46 publications

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“…The content of IL-1β ( Figure S8 B) and IL-18 ( Figure S8 C) in tumor homogenate also confirmed this result. Previous studies have shown that pyroptosis can induce anti-tumor immune responses 36 , 37 . To investigate the in vivo immune effect, cells from tumor tissues and tumor-draining lymph node (TDLN) tissues were collected to detect the proportion of immune cells using flow cytometry.…”

Section: Resultsmentioning

confidence: 99%

Sonodynamic-immunomodulatory nanostimulators activate pyroptosis and remodel tumor microenvironment for enhanced tumor immunotherapy

Chen¹,

Liu²,

Zuo³

et al. 2023

Theranostics

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Rationale: Spatiotemporal control of pyroptosis has a profound impact on cancer immunotherapy. Owing to the precise spatiotemporal control and reduction in the side effects of ultrasound (US), sonodynamic therapy (SDT) is expected to be a promising mean to activate pyroptosis. Furthermore, the pyroptosis-initiated immune response can be amplified by enhanced lymphocyte infiltration occurring due to extracellular matrix (ECM) depletion. Therefore, it is highly desirable to develop a sonodynamic-immunomodulatory strategy to amplify pyroptosis-mediated tumor immunotherapy by remodeling of the tumor microenvironment, thereby enhancing tumor immunotherapy. Methods: We reported a potent strategy based on a sonosensitizer, which is composed of LY364947-loaded porous coordination network (PCN-224) camouflaged with a red blood cell (RBC) membrane and evaluated pyroptosis activation, collagen depletion, immunocyte infiltration, and adaptive immune response during the pyroptosis-initiated immune response in vitro and in vivo . Results: The sonosensitizer generated reactive oxygen species (ROS) under US irradiation and initiated the caspase-3 apoptotic signaling pathway, which is regarded as the key upstream activator of gasdermin E (GSDME)-mediated pyroptosis. During the subsequent anti-tumor immune response mediated by pyroptosis, LY364947 loosened the ECM structure via collagen depletion, resulting in enhanced T-lymphocyte infiltration and nearly complete eradication of tumors in a mouse model with the formation of immunological memory. Conclusion: Our findings indicate that sonodynamic-immunomodulatory pyroptotic strategy exhibits robust anti-tumor immune efficacy as well as provides novel insights into the role of pyroptosis in cancer immunology.

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Section: Resultsmentioning

confidence: 99%

Sonodynamic-immunomodulatory nanostimulators activate pyroptosis and remodel tumor microenvironment for enhanced tumor immunotherapy

Chen¹,

Liu²,

Zuo³

et al. 2023

Theranostics

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“…To the best of our knowledge, tumor cells can mediate tumor immune escape by utilizing the PD1 / PDL1 checkpoint [ 76 , 77 ]. Interestingly, recent studies suggested that pyroptosis-induced inflammation could activate anti-tumor immune responses and sensitize cancer cells to anti-PD-1 therapy [ 78 , 79 ]. More importantly, KEGG analysis revealed that PD-L1 expression and PD-1 checkpoint pathway in cancer was enriched in the high-risk group.…”

Section: Discussionmentioning

confidence: 99%

A pyroptosis-related gene signature provides an alternative for predicting the prognosis of patients with hepatocellular carcinoma

et al. 2023

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Background Hepatocellular Carcinoma (HCC) is a common malignant neoplasm with limited treatment options and poor outcomes. Thus, there is an urgent need to find sensitive biomarkers for HCC. Methods Gene expression and clinicopathological information were obtained from public databases, based on which a pyroptosis-related gene signature was constructed by the least absolute shrinkage and selection operator Cox regression. The applicability of the signature was evaluated via Kaplan–Meier curve and time-dependent ROC curve. TIMER, QUANTISEQ, MCPCOUNTER, EPIC, CIBERSORT, ssGSEA, and ESTIMATE were employed to assess the immune status. Comparisons between groups were analyzed with Wilcoxon test. Pearson and Spearman correlation analyses were adopted for linear correlation analysis. Genetic knockdown was conducted using siRNA transfection and the mRNA expression levels of interest genes were measured using quantitative reverse transcription PCR. Finally, protein levels in 10 paired tumor tissues and adjacent non-tumor tissues from HCC patients were measured using immunohistochemistry. Results A pyroptosis-related gene signature was established successfully to calculate independent prognostic risk scores. It was found that survival outcomes varied significantly between different risk groups. In addition, an attenuated antitumor immune response was found in the high-risk group. Meanwhile, multiple immune checkpoints were up-regulated in high-risk score patients. Cell cycle-related genes, angiogenesis-related genes and tumor drug resistance genes were also markedly elevated. Knockdown of prognostic genes in the signature significantly inhibited the expression of immune checkpoint genes and angiogenesis-related genes. Besides, each prognostic gene was expressed at a higher level in HCC tissues than in adjacent normal tissues. Conclusions We successfully established a novel pyroptosis-related gene signature which could help predict the overall survival and assess the immune status of HCC patients.

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“…The tumor volume was measured every 3 days. This was then calculated as follows: V = (length) × (width) 2 /2 (Zhang et al., 2022 ).…”

Section: Methodsmentioning

confidence: 99%

Arenobufagin-loaded PEG-PLA nanoparticles for reducing toxicity and enhancing cancer therapy

et al. 2023

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Arenobufagin (ArBu) is a natural anticancer drug with good anti-tumor effects, but its clinical applications and drug development potential are limited due to its toxicity. The purpose of this study is to reduce the toxic side effects of ArBu and improve the efficacy of tumor treatment by incorporating it into poly(ethylene glycol)-b-poly (lactide) co-polymer (PEG-PLA). ArBu@PEG-PLA micelles were prepared by a thin film hydration method. The optimized micelles were characterized by size, stability, drug loading, encapsulation rate, and drug release. The tumor-inhibition efficacy of the micelles was evaluated on A549 cells and tumor-bearing mice. The ArBu@PEG-PLA micelles have good drug-loading capacity, release performance, and stability. They can accumulate at the tumor site through the EPR effect. The micelles induce apoptosis through a mitochondrial apoptosis pathway. Compared with the free ArBu, the ArBu@PEG-PLA micelles had lower toxicity and higher safety in the acute toxicity evaluation experiment. The in vivo anti-tumor experiment with tumor-bearing mice showed that the tumor-inhibition rate of ArBu@PEG-PLA micelles was 72.9%, which was 1.28-fold higher than that of free ArBu (57.1%), thus showing a good tumor treatment effect. This study indicates that ArBu@PEG-PLA polymeric micelles can significantly improve the toxicity and therapeutic efficacy of ArBu. These can lead to a new therapeutic strategy to reduce the toxicity of ArBu and enhance tumor treatment.

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Biomineralized Two‐Enzyme Nanoparticles Regulate Tumor Glycometabolism Inducing Tumor Cell Pyroptosis and Robust Antitumor Immunotherapy

Cited by 90 publications

References 46 publications

Sonodynamic-immunomodulatory nanostimulators activate pyroptosis and remodel tumor microenvironment for enhanced tumor immunotherapy

Sonodynamic-immunomodulatory nanostimulators activate pyroptosis and remodel tumor microenvironment for enhanced tumor immunotherapy

A pyroptosis-related gene signature provides an alternative for predicting the prognosis of patients with hepatocellular carcinoma

Arenobufagin-loaded PEG-PLA nanoparticles for reducing toxicity and enhancing cancer therapy

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