Immunogenic Cell Death Activates the Tumor Immune Microenvironment to Boost the Immunotherapy Efficiency

Advanced Science, Год журнала: 2022, Номер 9(22)

Опубликована: Июнь 2, 2022

Abstract Tumor immunotherapy is only effective in a fraction of patients due to low response rate and severe side effects, these challenges clinics can be addressed through induction immunogenic cell death (ICD). ICD elicited from many antitumor therapies release danger associated molecular patterns (DAMPs) tumor‐associated antigens facilitate maturation dendritic cells (DCs) infiltration cytotoxic T lymphocytes (CTLs). The process reverse the tumor immunosuppressive microenvironment improve sensitivity immunotherapy. Nanostructure‐based drug delivery systems (NDDSs) are explored induce by incorporating therapeutic molecules for chemotherapy, photosensitizers (PSs) photodynamic therapy (PDT), photothermal conversion agents (PTT), radiosensitizers radiotherapy (RT). These NDDSs loaded at right dose place time, resulting greater effectiveness lower toxicity. Immunotherapeutic also combined with achieve synergic effect multi‐modality approach. In this review, harnessed load multiple PDT, PTT, RT combination promote reduce effects cancer treatment.

Язык: Английский

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Transformable Nanosensitizer with Tumor Microenvironment‐Activated Sonodynamic Process and Calcium Release for Enhanced Cancer Immunotherapy

Angewandte Chemie International Edition, Год журнала: 2021, Номер 60(25), С. 14051 - 14059

Опубликована: Апрель 2, 2021

Abstract Despite the promise of sonodynamic processes in cancer therapy, existing sonosensitizers often fail to regulate generation reactive oxygen species (ROS) against tumors, potentially leading off‐target toxicity normal tissues. We report a transformable core‐shell nanosonosensitizer (TiO 2 @CaP) that reinvigorates ROS and dissolves its CaP shell release Ca 2+ an acidic tumor microenvironment (TME) under ultrasound activation. Thus, TiO @CaP acts as smart specifically induces mitochondrial dysfunction via overloading intracellular ions synergize with process TME. substantially enhances immunogenic cell death, resulting enhanced T‐cell recruitment infiltration into cold (4T1). In conjunction checkpoint blockade therapy (anti‐PD 1), @CaP‐mediated elicits systemic antitumor immunity, regression non‐treated distant tumors inhibition lung metastasis. This work paves way development “smart” TME‐activatable temporospatial control over responses.

Язык: Английский

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ZIF‐8 Nanoparticles Evoke Pyroptosis for High‐Efficiency Cancer Immunotherapy

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(10)

Опубликована: Янв. 11, 2023

Although zeolitic imidazolate framework-8 (ZIF-8) has been applied in various tumor therapies, the intrinsic immunogenicity remains unclear. Here, we initiatively discover that ZIF-8 nanoparticles (NPs) can intrinsically induce pyroptosis by a caspase-1/gasdermin D (GSDMD)-dependent pathway. The pyroptotic cell death is accompanied necrosis and immunogenic (ICD) simultaneously for efficient situ immunity initiation. Meanwhile, carbonyl cyanide m-chlorophenyl hydrazone (CCCP), mitochondrial depolarizing agent, successfully loaded into NPs found to further enhance process. Collectively, obtained Pluronic F127-modified CCCP-incorporated (F127 ZIF-8CCCP NPs) activate antitumor reprogram immunosuppressive microenvironment (TME), realizing high-efficiency growth inhibition. This work will facilitate biomedicine applications of provide good inspiration pyroptosis-induced cancer therapy.

Язык: Английский

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Stimuli‐Responsive Nanoparticles for Controlled Drug Delivery in Synergistic Cancer Immunotherapy

Advanced Science, Год журнала: 2021, Номер 9(5)

Опубликована: Дек. 19, 2021

Cancer immunotherapy has achieved promising clinical progress over the recent years for its potential to treat metastatic tumors and inhibit their recurrences effectively. However, low patient response rates dose-limiting toxicity remain as major dilemmas immunotherapy. Stimuli-responsive nanoparticles (srNPs) combined with offer possibility amplify anti-tumor immune responses, where weak acidity, high concentration of glutathione, overexpressions enzymes, reactive oxygen species, external stimuli in act triggers controlled drug release. This review highlights design srNPs based on tumor microenvironment and/or combine different drugs, especially immunoregulatory agents, which eventually realize synergistic malignant primary or acquire a long-term memory prevent recurrence. The authors hope that this can provide theoretical guidance construction transformation smart delivery cancer

Язык: Английский

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Metal-based anticancer agents as immunogenic cell death inducers: the past, present, and future

Chemical Society Reviews, Год журнала: 2022, Номер 51(4), С. 1212 - 1233

Опубликована: Янв. 1, 2022

Cancer is the deadliest disease in world behind heart disease. Sadly, this remains true even as we suffer ravages of Covid-19 pandemic. Whilst current chemo- and radiotherapeutic treatment strategies have significantly improved patient survival rate, reoccurrence continues to pose a deadly risk for all too many patients. Incomplete removal tumour cells from body increases chances metastasis developing resistance against treatments. Immunotherapy represents therapeutic modality that has helped overcome these limitations recent decades. However, further progress needed. So-called immunogenic cell death (ICD) recently discovered unique mode could trigger necessary progress. ICD involves stimulation tumour-specific immune response downstream effect. Facilitated by certain modalities, undergoing can IFN-γ mediated involving cytotoxic T (CTLs) γδ eradicate residual cells. In years, there been significant increase number small-molecules being tested potential inducers. A large inducers are metal-based complexes. fact, anticancer metal drugs based on Pt, Ru, Ir, Cu, Au now known give rise an result ICD. Advances also made terms exploiting combinatorial delivery strategies. favourable cases, approaches shown efficacy otherwise "silent" Taken concert, rationally designed novel complexes act show promise new immunotherapies neoplastic This Tutorial Review will allow readers assess fast-evolving field thus setting stage future advances.

Язык: Английский

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Biodegradable Ca²⁺ Nanomodulators Activate Pyroptosis through Mitochondrial Ca²⁺ Overload for Cancer Immunotherapy

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(36)

Опубликована: Июнь 10, 2022

Abstract Pyroptosis provides a new direction and broad prospects for cancer immunotherapy. However, the development of nanoplatform as pyroptosis inducer is limited, discovery type nano‐pyroptosis immunotherapy still imminent. Herein, biodegradable Ca 2+ nanomodulators (CaNMs) are prepared inducers via mitochondrial overload. The obtained CaNMs can decompose under low pH to release curcumin, leading sudden surge in ions, eventually resulting pyroptosis. We not only confirm occurrence overload‐triggered first time but also reveal robust immune responses CaNMs, along with remarkably suppressing tumor proliferation lung metastasis. This work will provide strategies inspiration pyroptosis‐mediated treatments, greatly contributing further nanomodulators.

Язык: Английский

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The Role of Tumor Inflammatory Microenvironment in Lung Cancer

Frontiers in Pharmacology, Год журнала: 2021, Номер 12

Опубликована: Май 17, 2021

Lung cancer is the most common and fatal malignant tumor in world. The microenvironment (TME) closely related to occurrence development of lung cancer, which inflammatory plays an important role. Inflammatory cells factors promote activation NF-κB STAT3 pathways occurrence, development, metastasis by promoting immune escape, angiogenesis, epithelial–mesenchymal transition, apoptosis, other mechanisms. Clinical epidemiological studies have also shown a strong relationship among chronic infection, inflammation, microenvironment, cancer. between inflammation can be better understood through gradual understanding advantageous find more therapeutic targets for

Язык: Английский

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Biodegradable Upconversion Nanoparticles Induce Pyroptosis for Cancer Immunotherapy

Nano Letters, Год журнала: 2021, Номер 21(19), С. 8281 - 8289

Опубликована: Сен. 30, 2021

Pyroptosis, which is a mode of programmed cell death, has proven effective for cancer therapy. However, efficient pyroptosis inducers tumor treatment are limited. This study proposes biodegradable K3ZrF7:Yb/Er upconversion nanoparticles (ZrNPs) as immunotherapy. ZrNPs, similar to ion reservoirs, can be dissolved inside cells and release high amounts K+ [ZrF7]3- ions, resulting surge in intracellular osmolarity homeostasis imbalance. further induces an increase reactive oxygen species (ROS), caspase-1 protein activation, gasdermin D (GSDMD) cleavage, interleukin-1β (IL-1β) maturity, results cytolysis. In vivo tests confirm that ZrNPs-induced exhibits superior antitumor immunity activity confirmed by enhanced dendritic (DCs) maturity frequency effector-memory T cells, well observably inhibiting growth pulmonary metastasis. work believed extend the biomedical applications nanomaterials deepen understanding intrinsic immunomodulatory nanomaterials.

Язык: Английский

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A “Closed‐Loop” Therapeutic Strategy Based on Mutually Reinforced Ferroptosis and Immunotherapy

Advanced Functional Materials, Год журнала: 2022, Номер 32(13)

Опубликована: Фев. 1, 2022

Abstract The immunosuppression and immune escape of current immunotherapy result in low efficacy, ferroptosis is greatly restricted by the reactive oxygen species (ROS) production efficiency. Here, for first time a “closed‐loop” therapy based on photothermal enhancement stimulated each other multifunctional nanoplatform reported. This platform composed copper silicate iron mesoporous hollow nanospheres, followed situ growth Au nanoparticles loading an adjuvant resiquimod R848. laser irradiation‐mediated heat introduction ions significantly enhance ROS generation, leading to simultaneous depletion glutathione peroxidase 4 (GPX4) (GSH). onset tumor cells thus enhanced response with immunogenic cell death (ICD) triggered, promoting dendritic (DCs) maturation T infiltration. Interferon γ (IFN‐γ) released from CD8 + downregulates expression SLC7A11 GPX4, which turn enhances expression, constituting “closed‐Loop” therapy. Importantly, this system effective both killing primary inhibiting metastasis. proposed therapeutic strategy may provide guidance design future antitumor nanoplatforms.

Язык: Английский

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Synergistic Reinforcing of Immunogenic Cell Death and Transforming Tumor‐Associated Macrophages Via a Multifunctional Cascade Bioreactor for Optimizing Cancer Immunotherapy

Advanced Materials, Год журнала: 2022, Номер 34(51)

Опубликована: Окт. 17, 2022

Immunogenic cell death (ICD) has aroused widespread attention because it can reconstruct a tumor microenvironment and activate antitumor immunity. This study proposes two-way enhancement of ICD based on CaO2 @CuS-MnO2 @HA (CCMH) nanocomposite to overcome the insufficient damage-associated molecular patterns (DAMPs) conventional ICD-inducers. The near-infrared (NIR) irradiation (1064 nm) CuS nanoparticles generates 1 O2 through photodynamic therapy (PDT) trigger ICD, also damages Ca2+ buffer function mitochondria. Additionally, react with H2 O produce large amount , which respectively lead enhanced PDT overload during mitochondrial damage, thereby triggering robust activation. Moreover, oxidative-damaged DNA, induced by released from cells, reprograms immunosuppressive transforming tumor-associated macrophages M1 subphenotype. shows that CCMH NIR-II elicit adequate DAMPs an active tumor-immune for both 4T1 CT26 models. Combining this method immune checkpoint blockade realize improved immunotherapy efficacy long-term protection effect body.

Язык: Английский

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