Biomimetic Nanophotosensitizer Amplifies Immunogenic Pyroptosis and Triggers Synergistic Cancer Therapy

Wang, Qian; Qin, Weiji; Qiao, Lei; Gao, Min; Zhou, Man; Zhang, Huiru; Sun, Qiuting; Yao, Wanqing; Yang, Tianhao; Ren, Xiaohe; Sun, Gengyun; He, Xiaoyan

doi:10.1002/adhm.202301641

Cited by 4 publications

(1 citation statement)

References 48 publications

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“…This fragment subsequently penetrated the cell membrane and caused immunogenic pyroptosis. Ultimately, the pyrolytic cells will release DMAPs, which induce ICD. ,, To further verify the mechanism involved in pyroptosis, changes in the mitochondrial membrane potential were first investigated. Here, a 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolyl-carbocyanine iodide (JC-1) kit was utilized to investigate the influence of I-L@NM on mitochondrial activity.…”

Section: Resultsmentioning

confidence: 99%

Advancing Precision: A Controllable Self-Synergistic Nanoplatform Initiating Pyroptosis-Based Immunogenic Cell Death Cascade for Targeted Tumor Therapy

Qin,

Qiao,

Wang

et al. 2024

ACS Nano

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Heterogeneity of the tumor microenvironment (TME) is primarily responsible for ineffective tumor treatment and uncontrolled tumor progression. Pyroptosis-based immunogenic cell death (ICD) therapy is an ideal strategy to overcome TME heterogeneity and obtain a satisfactory antitumor effect. However, the efficiency of current pyroptosis therapeutics, which mainly depends on a single endogenous or exogenous stimulus, is limited by the intrinsic pathological features of malignant cells. Thus, it is necessary to develop a synergistic strategy with a high tumor specificity and modulability. Herein, a synergistic nanoplatform is constructed by combining a neutrophil camouflaging shell and a selfsynergistic reactive oxygen species (ROS) supplier-loaded polymer. The covered neutrophil membranes endow the nanoplatform with stealthy properties and facilitate sufficient tumor accumulation. Under laser irradiation, the photosensitizer (indocyanine green) exogenously triggers ROS generation and converts the laser irradiation into heat to upregulate NAD(P)H:quinone oxidoreductase 1, which further catalyzes β-Lapachone to self-produce sufficient endogenous ROS, resulting in amplified ICD outcomes. The results confirm that the continuously amplified ROS production not only eliminates the primary tumor but also concurrently enhances gasdermin E-mediated pyroptosis, initiates an ICD cascade, re-educates the heterogeneous TME, and promotes a systemic immune response to suppress distant tumors. Overall, this self-synergistic nanoplatform provides an efficient and durable method for redesigning the immune system for targeted tumor inhibition.

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Section: Resultsmentioning

confidence: 99%

Advancing Precision: A Controllable Self-Synergistic Nanoplatform Initiating Pyroptosis-Based Immunogenic Cell Death Cascade for Targeted Tumor Therapy

Qin,

Qiao,

Wang

et al. 2024

ACS Nano

Self Cite

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Lysosomal Rupture‐Mediated “Broken Window Effect” to Amplify Cuproptosis and Pyroptosis for High‐Efficiency Cancer Immunotherapy

Zhu,

Wang,

Qiao

et al. 2024

Adv Funct Materials

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Autophagy, a lysosome‐involved degradation pathway, as a self‐protective cellular process, always weakens the efficiency of tumor therapies. Herein, for the first time, the biodegradable copper (Cu) ions doped layered double hydroxide (Cu‐LDH) nanoparticles are reported for cancer immunotherapy via lysosomal rupture‐mediated “Broken Window Effect”. Only injection of Cu‐LDH single therapeutic agent achieves various organelles destruction after lysosomal rupture, as well as the abnormal aggregation of Cu ions in tumor cells for cuproptosis and pyroptosis. More importantly, autophagy inhibition caused by lysosomal rupture improves Cu ions overload‐mediated cuproptosis and pyroptosis by blocking the lysosome‐mediated bulk degradation pathway, leading to good anti‐tumor immune responses and ultimately high‐efficiency tumor growth inhibition. This lysosomal rupture‐mediated “Broken Window Effect” provides a new paradigm for the autophagy enhanced tumor therapy.

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Engineering Bimetallic Polyphenol for Mild Photothermal Osteosarcoma Therapy and Immune Microenvironment Remodeling by Activating Pyroptosis and cGAS‐STING Pathway

Liu,

Zan,

et al. 2024

Adv Healthcare Materials

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The immunosuppressive tumor microenvironment (ITME) of osteosarcoma (OS) poses a significant obstacle to the efficacy of existing immunotherapies. Despite the attempt of novel immune strategies such as immune checkpoint inhibitors and tumor vaccines, their effectiveness remains suboptimal due to the inherent difficulty in mitigating ITME simultaneously from both the tumor and immune system. The promotion of anti‐tumor immunity through the induction of immunogenic cell death and activation of the cGAS‐STING pathway has emerged as potential strategies to counter the ITME and stimulate systemic antitumor immune responses. Here we present a bimetallic polyphenol‐based nanoplatform (Mn/Fe‐Gallate nanoparticles coated with tumor cell membranes, MFG@TCM) which combines with mild photothermal therapy (PTT) for reversing ITME via simultaneously inducing pyroptosis in OS cells and activating the cGAS‐STING pathway in dendritic cells (DCs). The immunostimulatory pathways, through the syngeneic effect, exerted a substantial positive impact on promoting the secretion of damage‐associated molecular patterns (DAMPs) and proinflammatory cytokines, which favors remodeling the immune microenvironment. Consequently, effector T cells led to a notable systemic antitumor immune response, effectively inhibiting the growth of both primary and distant tumors. This study offers a comprehensive approach to treat OS by mild photothermal therapy and modulating the immune microenvironment, exhibiting considerable potential in addressing the constraints associated with current therapeutic modalities.This article is protected by copyright. All rights reserved

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Biomimetic Nanophotosensitizer Amplifies Immunogenic Pyroptosis and Triggers Synergistic Cancer Therapy

Cited by 4 publications

References 48 publications

Advancing Precision: A Controllable Self-Synergistic Nanoplatform Initiating Pyroptosis-Based Immunogenic Cell Death Cascade for Targeted Tumor Therapy

Advancing Precision: A Controllable Self-Synergistic Nanoplatform Initiating Pyroptosis-Based Immunogenic Cell Death Cascade for Targeted Tumor Therapy

Lysosomal Rupture‐Mediated “Broken Window Effect” to Amplify Cuproptosis and Pyroptosis for High‐Efficiency Cancer Immunotherapy

Engineering Bimetallic Polyphenol for Mild Photothermal Osteosarcoma Therapy and Immune Microenvironment Remodeling by Activating Pyroptosis and cGAS‐STING Pathway

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