Ultrasound-Augmented Mitochondrial Calcium Ion Overload by Calcium Nanomodulator to Induce Immunogenic Cell Death

Nano Letters, Journal Year: 2021, Volume and Issue: 21(5), P. 2088 - 2093

Published: Feb. 17, 2021

Immunogenic cell death (ICD), a manner of tumor that can trigger antitumor immune responses, has received extensive attention as potential synergistic modality for cancer immunotherapy. Although many calcium ion (Ca2+) nanomodulators have been developed therapy through mitochondrial Ca2+ overload, their ICD-inducing properties not explored. Herein, an acid-sensitive PEG-decorated carbonate (CaCO3) nanoparticle incorporating curcumin (CUR; enhancer) (PEGCaCUR) was prepared using simple one-pot strategy. PEGCaCUR served only nanomodulator inducing efficient overload but also ICD inducer during improved therapy. Combination with ultrasound (US), PEGCaCUR+US, led to enhanced effect attributable the along subsequent upregulation reactive oxygen species levels. facilitates photoacoustic/fluorescence dual-mode imaging, well effectively suppressing growth and metastasis, indicating promising theranostic properties.

Language: Английский

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Immunogenic Cell Death Induction by Ionizing Radiation

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Aug. 20, 2021

Immunogenic cell death (ICD) is a form of regulated (RCD) induced by various stresses and produces antitumor immunity via damage-associated molecular patterns (DAMPs) release or exposure, mainly including high mobility group box 1 (HMGB1), calreticulin (CRT), adenosine triphosphate (ATP), heat shock proteins (HSPs). Emerging evidence has suggested that ionizing radiation (IR) can induce ICD, the dose, type, fractionation irradiation influence induction ICD. At present, IR-induced ICD verified in vitro mice there few clinical about it. To boost IR, some strategies have shown synergy with IR to enhance immune response, such as hyperthermia, nanoparticles, chemotherapy. In this review, we focus on mechanisms ICD-promoting factors associated irradiation, immunogenic forms death. Finally, summarize methods improving IR.

Language: Английский

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

Chemical Society Reviews, Journal Year: 2022, Volume and Issue: 51(4), P. 1212 - 1233

Published: Jan. 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.

Language: Английский

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Photodecaging of a Mitochondria-Localized Iridium(III) Endoperoxide Complex for Two-Photon Photoactivated Therapy under Hypoxia

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(9), P. 4091 - 4101

Published: Feb. 16, 2022

Despite the clinical success of photodynamic therapy (PDT), application this medical technique is intrinsically limited by low oxygen concentrations found in cancer tumors, hampering production therapeutically necessary singlet (1O2). To overcome limitation, we report on a novel mitochondria-localized iridium(III) endoperoxide prodrug (2-O-IrAn), which, upon two-photon irradiation NIR, synergistically releases highly cytotoxic complex (2-IrAn), oxygen, and an alkoxy radical. 2-O-IrAn was to be (photo-)toxic hypoxic tumor cells multicellular spheroids (MCTS) nanomolar range. provide selectivity improve pharmacological properties 2-O-IrAn, it encapsulated into biotin-functionalized polymer. The generated nanoparticles were nearly fully eradicate inside mouse model within single treatment. This study presents, best our knowledge, first example iridium(III)-based for synergistic therapy/photoactivated chemotherapy, opening up new avenues treatment tumors.

Language: Английский

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Golgi apparatus-targeted aggregation-induced emission luminogens for effective cancer photodynamic therapy

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: April 21, 2022

Abstract Golgi apparatus (GA) oxidative stress induced by in situ reactive oxygen species (ROS) could severely damage the morphology and function of GA, which may open up an avenue for effective photodynamic therapy (PDT). However, due to lack design strategy, photosensitizers (PSs) with specific GA targeting ability are high demand yet quite challenging. Herein, we report aggregation-induced emission luminogen (AIEgen) based PS (TPE-PyT-CPS) that can effectively target via caveolin/raft mediated endocytosis a Pearson correlation coefficient 0.98. Additionally, introduction pyrene into TPE-PyT-CPS reduce energy gap between lowest singlet state (S 1 ) triplet (T (Δ E ST exhibits enhanced generation capability. fragmentation cleavage proteins (p115/GM130) observed upon light irradiation. Meanwhile, apoptotic pathway is activated through crosstalk mitochondria HeLa cells. More importantly, TPE-T-CPS show better PDT effect than its non-GA-targeting counterpart TPE-PyT-PS, even though they possess very close ROS rate. This work provides strategy development PSs ability, great importance precise PDT.

Language: 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, Journal Year: 2022, Volume and Issue: 34(51)

Published: Oct. 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.

Language: Английский

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Ferroptosis‐Enhanced Cancer Immunity by a Ferrocene‐Appended Iridium(III) Diphosphine Complex

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 61(16)

Published: Dec. 29, 2021

Ferroptosis is a programmed cell death pathway discovered in recent years, and ferroptosis-inducing agents have great potential as new antitumor candidates. Here, we report IrIII complex (Ir1) containing ferrocene-modified diphosphine ligand that localizes lysosomes. Under the acidic environments of lysosomes, Ir1 can effectively catalyze Fenton-like reaction, produce hydroxyl radicals, induce lipid peroxidation, down-regulate glutathione peroxidase 4, result ferroptosis. RNA sequencing analysis shows significantly affect pathways related to ferroptosis cancer immunity. Accordingly, immunogenic cells suppress tumor growth vitro, regulate T activity immune microenvironments vivo. In conclusion, show small molecules with capabilities for effective immunotherapy.

Language: Английский

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Nitric Oxide Induces Immunogenic Cell Death and Potentiates Cancer Immunotherapy

ACS Nano, Journal Year: 2022, Volume and Issue: 16(3), P. 3881 - 3894

Published: March 3, 2022

Tumor cells undergoing immunogenic cell death (ICD) release damage-associated molecular patterns (DAMPs) to trigger a long-term protective antitumor response. ICD can be induced by certain pathogens, chemotherapeutics, and physical modalities. In this work, we demonstrate that gaseous molecule, specifically nitric oxide (NO), induce potent effect. NO exerts cytotoxic effects are accompanied the emission of DAMPs based on endoplasmic reticulum stress mitochondrial dysfunction pathways. Released elicit immunological protection against subsequent rechallenge syngeneic tumor in immunocompetent mice. We prepare polynitrosated polyesters with high storage capacity through facile polycondensation reaction followed postsynthetic modification. The polyesters-based nanogenerator (NanoNO) enables efficient delivery controlled tumors induces sufficient different immune-intact models tumors, NanoNO exhibits significant growth suppression increases local dose signals T infiltrations, ultimately prolonging survival. addition, synergizes PD-1 blockade prevent metastasis. conclude not only is inducer for cancer immunotherapy but also it expands range inducers into field molecules.

Language: Английский

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Immunogenic Cell Death Inducing Metal Complexes for Cancer Therapy

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(21)

Published: Feb. 21, 2023

Cancer is one of the deadliest diseases worldwide. Recent statistics have shown that metastases and tumor relapse are leading causes cancer-associated deaths. While traditional treatments able to efficiently remove primary tumor, secondary tumors remain poorly accessible. Capitalizing on this there an urgent need for novel treatment modalities. Among most promising approaches, increasing research interest has been devoted immunogenic cell death inducing agents trigger localized cancer cells as well induce immune response inside whole organism. Preliminary studies compounds could be overcome metastatic relapsing tumors. Herein, application metal complexes systematically reviewed.

Language: Английский

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GSH-Responsive Nanoprodrug to Inhibit Glycolysis and Alleviate Immunosuppression for Cancer Therapy

Nano Letters, Journal Year: 2021, Volume and Issue: 21(18), P. 7862 - 7869

Published: Sept. 8, 2021

Blocking energy metabolism of cancer cells and simultaneously stimulating the immune system to perform attack are significant for treatment. However, how potently deliver different drugs with these functions remains a challenge. Herein, we synthesized nanoprodrug formed by F127-coated drug dimer inhibit glycolysis alleviate immunosuppressive microenvironment. The was delicately constructed connect lonidamine (LND) NLG919 disulfide bond which can be cleaved excess GSH release two drugs. LND decrease expression hexokinase II destroy mitochondria restrain supply. reduce accumulation kynurenine number regulatory T cells, thus alleviating Notably, consumption increased intracellular oxidative stress triggered immunogenic cell death cells. This strategy offer more possibilities explore dimeric prodrugs synergistic therapy.

Language: Английский

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