A pyroptosis nanotuner for cancer therapy

Chen, Binlong; Yan, Yue; Yang, Yunliu; Cao, Guang; Wang, Xiao; Wang, Yaoqi; Wan, Fangjie; Yin, Qingqing; Wang, Zenghui; Li, Yunfei; Wang, Letong; Xu, Bo; You, Fangtian; Zhang, Qiang; Wang, Yiguang

doi:10.1038/s41565-022-01125-0

Cited by 126 publications

(94 citation statements)

References 38 publications

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“…Pyroptosis is a newly disclosed manner of immunogenic cell death, leading to the release of multiple pro-inflammatory cytokines and alarmins from dying cells, which then trigger robust antigen specific immune responses [ 17 – 19 ]. Gasdermin family proteins are key executors of pyroptosis, wherein the gasdermin D (GSDMD) is cleaved by Caspase-1 to form its N-terminal domain (GSDMD-N), which then binds with cellular membrane phospholipids and drills pores on cell membranes.…”

Section: Introductionmentioning

confidence: 99%

A mitochondria-anchored supramolecular photosensitizer as a pyroptosis inducer for potent photodynamic therapy and enhanced antitumor immunity

et al. 2022

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Background The discovery of a potent photosensitizer with desirable immunogenic cell death (ICD) ability can prominently enhance antitumor immunity in photodynamic therapy (PDT). However, majority of commercially-available photosensitizers suffer from serious aggregation and fail to elicit sufficient ICD. Pyroptosis as a newly identified pattern for potent ICD generation is rarely disclosed in reported photosensitizers. In addition, the photosensitizer with excellent mitochondria-anchored ability evokes prominent mitochondria oxidative stress, and consequently induces ICD. Results Herein, a novel supramolecular photosensitizer LDH@ZnPc is reported, without complicated preparation, but reveals desirable pyroptosis-triggered ability with mitochondria anchoring feature. LDH@ZnPc is obtained through isolation of ZnPc using positive charged layered double hydroxides (LDH), and excellent mitochondria-anchored ability is achieved. More importantly, LDH@ZnPc-mediated PDT can effectively initiate gasdermin D (GSDMD)-dependent pyroptosis of tumor cells. In vitro and in vivo results verify robust ICD ability and potent tumor inhibition efficacy, and antitumor immunity towards distant tumor inhibition. Conclusions This study reveals that LDH@ZnPc can act as an excellent pyroptosis inducer with simultaneous mitochondria anchoring ability for enhancing photodynamic therapy and boosting antitumor immunity. Graphical Abstract

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Section: Introductionmentioning

confidence: 99%

A mitochondria-anchored supramolecular photosensitizer as a pyroptosis inducer for potent photodynamic therapy and enhanced antitumor immunity

et al. 2022

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“…According to the conserved N-terminal and C-terminal regions, six homologous members of the gasdermin family have been found in humans, namely GSDMA, GSDMB, GSDMC, GSDMD, GSDME, and PJVK 27 . Recently, pyroptosis is renamed as gasdermin-mediated programmed necrosis since the gasdermin family of pore-forming proteins play a key role in the process 28 . Pyroptosis, characterized by rapid membrane rupture, cell swelling with large bubbles and release of cellular proinflammatory contents, plays vital pathophysiological roles in atherosclerosis, diabetics, pathogen infections, and organ failures 29 .…”

Section: Discussionmentioning

confidence: 99%

A comprehensive analysis of gasdermin family gene as therapeutic targets in pan-cancer

Huo

Deng

Sun

2022

Sci Rep

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Six members of the gasdermin family are involved in various biological functions in malignant tumors. The present study aimed to perform a comprehensive analysis of gasdermin family genes in pan-cancer. Raw data was acquired from the genotype-tissue expression (GTEx) and the Cancer Genome Atlas. High inter-tumor heterogeneity in the expression between paracancerous and tumor tissues was observed across cancers. Survival analysis confirmed that the risk or protective effects of gasdermin family members on prognosis depended on the cancer types. The mutation frequency appeared to be high, and the mutation group had a worse prognosis. Besides, gasdermin family genes were associated with immune infiltrate subtypes, stromal and immune cell infiltration levels, TMB, MSI, immune checkpoint gene expression, and tumor stemness scores. Moreover, gasdermin family gene expressions affected the expressions of MMR genes and methyltransferases and could predict cancer cells sensitivity to chemotherapeutic drugs. Subsequently, the findings were double-checked in LIHC and PAAD. GSEA results indicated the gasdermin family genes mainly involved in tumor metabolism and immune microenvironment remodeling related signaling pathways. In conclusion, our findings confirmed that gasdermin family genes were potential therapeutic cancer targets in pan-cancer.

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“…Very recently, an acid‐activatable nanophotosensitizer (ANPS) library (based on mPEG‐bP(R1‐rR2)) was fabricated with a visible pH transition (pHt) from 5.3 to 6.9, covering the whole pH range of the endosomal maturation process ( Figure 22 ). [ 69 ] The developed ultra‐pH‐sensitive nanoparticles could trigger an extensive GSDME‐mediated pyroptotic pathway through phospholipase C (PLC) activation caused by PDT‐induced oxidative stress in early endosomes (pH 6.8–6.1). In contrast, the pyroptotic activity was dramatically inhibited in late endosomes (pH 6.1–5.5) and lysosomes (pH 5.5–4.5), which was resulted from the PLC absence and cathepsin B inactivation in late endosomes and late lysosomes stages.…”

Section: Pyroptosis Induced By Other Approachesmentioning

confidence: 99%

Nanomedicine‐Enabled/Augmented Cell Pyroptosis for Efficient Tumor Nanotherapy

et al. 2022

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The terrible morbidity and mortality of malignant tumors urgently require innovative therapeutics, especially for apoptosis‐resistant tumors. Pyroptosis, a pro‐inflammatory form of programmed cell death (PCD), is featured with pore formation in plasma membrane, cell swelling with giant bubbles, and leakage of cytoplasmic pro‐inflammatory cytokines, which can remodel the tumor immune microenvironment by stimulating a “cold” tumor microenvironment to be an immunogenic “hot” tumor microenvironment, and consequently augment the therapeutic efficiency of malignant tumors. Benefiting from current advances in nanotechnology, nanomedicine is extensively applied to potentiate, enable, and augment pyroptosis for enhancing cancer‐therapeutic efficacy and specificity. This review provides a concentrated summary and discussion of the most recent progress achieved in this emerging field, highlighting the nanomedicine‐enabled/augmented specific pyroptosis strategy for favoring the construction of next‐generation nanomedicines to efficiently induce PCD. It is highly expected that the further clinical translation of nanomedicine can be accelerated by inducing pyroptotic cell death based on bioactive nanomedicines.

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A pyroptosis nanotuner for cancer therapy

Cited by 126 publications

References 38 publications

A mitochondria-anchored supramolecular photosensitizer as a pyroptosis inducer for potent photodynamic therapy and enhanced antitumor immunity

A mitochondria-anchored supramolecular photosensitizer as a pyroptosis inducer for potent photodynamic therapy and enhanced antitumor immunity

A comprehensive analysis of gasdermin family gene as therapeutic targets in pan-cancer

Nanomedicine‐Enabled/Augmented Cell Pyroptosis for Efficient Tumor Nanotherapy

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