Mn-based cGAS-STING activation for tumor therapy

Chinese Journal of Cancer Research, Journal Year: 2023, Volume and Issue: 35(1), P. 19 - 43

Published: Jan. 1, 2023

Immunotherapy has efficiently revolutionized the treatment of human neoplastic diseases. However, overall responsive rate current immunotherapy is still unsatisfactory, benefiting only a small proportion patients. Therefore, significant attention been paid to modulation tumor microenvironment (TME) for enhancement immunotherapy. Interestingly, recent studies have shown that cyclic GMP-AMP synthase-stimulator interferon gene (cGAS-STING) was initially found as an innate immune sensor recognize cytoplasmic DNA (such bacterial, viral, micronuclei, and mitochondrial). It promising signaling pathway activate antitumor responses via type I production. Notably, Mn2+ be critical molecule sensitize activation cGAS-STING better This led development Mn2+-based strategies pathway. In this review, we aimed summarize progress field, focusing on following three aspects. First, briefly introduced activation, its regulation effect immunity cycle discussed. Along with this, several agonists were their potential immunotherapeutic drugs. Then, basic biological functions illustrated, roles in activation. Next, systematically reviewed immunotherapy, which can classified by methods based alone or combined other therapeutic modalities. We finally speculated future perspectives field provided rational suggestions develop therapeutics.

Language: Английский

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Designing a Mitochondria-Targeted Theranostic Cyclometalated Iridium(III) Complex: Overcoming Cisplatin Resistance and Inhibiting Tumor Metastasis through Necroptosis and Immune Response

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(5), P. 3843 - 3859

Published: March 5, 2024

To develop a potential theranostic metal agent to reverse the resistance of cancer cells cisplatin and effectively inhibit tumor growth metastasis, we proposed design cyclometalated iridium (Ir) complex based on properties environment (TME). end, designed synthesized series Ir(III) 2-hydroxy-1-naphthaldehyde thiosemicarbazone complexes by modifying hydrogen atom(s) N-3 position compounds structure dimers then investigated their structure–activity structure–fluorescence relationships obtain an (Ir5) with remarkable fluorescence cytotoxicity cells. Ir5 not only possesses mitochondria-targeted but also overcomes inhibits metastasis in vivo. Besides, confirmed anticancer mechanisms acting different components TME: directly killing liver inducing necroptosis activating necroptosis-related immune response.

Language: Английский

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A Bioactive Injectable Hydrogel Regulates Tumor Metastasis and Wound Healing for Melanoma via NIR‐Light Triggered Hyperthermia

Advanced Science, Journal Year: 2024, Volume and Issue: 11(26)

Published: May 5, 2024

Abstract Surgical resection remains the mainstream treatment for malignant melanoma. However, challenges in wound healing and residual tumor metastasis pose significant hurdles, resulting high recurrence rates patients. Herein, a bioactive injectable hydrogel (BG‐Mn gel ) formed by crosslinking sodium alginate (SA) with manganese‐doped glass (BG‐Mn) is developed as versatile platform anti‐tumor immunotherapy postoperative The incorporation of Mn 2+ within (BG) can activate cGAS‐STING immune pathway to elicit robust response cancer immunotherapy. Furthermore, doping BG endows system excellent photothermal properties, hence facilitating STING activation reversing immune‐suppressive microenvironment. exhibits favorable angiogenic capacity tissue regenerative potential, promotes cell migration vitro. When combining BG‐Mn anti‐PD‐1 antibody (α‐PD‐1) melanoma, it shows enhanced long‐term memory response. Remarkably, upregulate expression genes related blood vessel formation promote skin regeneration when treating full‐thickness wounds. Overall, Gel serves an effective adjuvant therapy regulate

Language: Английский

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Biometallic ions and derivatives: a new direction for cancer immunotherapy

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 15, 2025

Biometallic ions play a crucial role in regulating the immune system. In recent years, cancer immunotherapy has become breakthrough treatment, achieving good efficacy wide range of cancers with its specificity and durability advantages. However, existing therapies still face challenges, such as tolerance escape. (e.g. zinc, copper, magnesium, manganese, etc.) can assist enhancing through activation cells, enhancement tumor antigen presentation, improvement microenvironment. addition, biometallic derivatives directly inhibit cell progression offer possibility effectively overcoming limitations current by promoting responses reducing immunosuppressive signals. This review explores potential application prospects immunotherapy, providing new ideas for future clinical metal part helping to guide development more effective safe therapeutic regimens.

Language: Английский

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Herpesvirus‐Mimicking DNAzyme‐Loaded Nanoparticles as a Mitochondrial DNA Stress Inducer to Activate Innate Immunity for Tumor Therapy

Advanced Materials, Journal Year: 2022, Volume and Issue: 34(37)

Published: July 23, 2022

Abstract Virus‐based immunotherapy is a promising approach to treat tumor. Closely mimicking the structure and sequential infection processes of natural viruses highly desirable for effective tumor but remains challenging. Here, inspired by robust innate immunity induced herpesvirus, herpesvirus‐mimicking nanoparticle (named Vir‐ZM@TD) engineered therapy herpesvirus. In this biomimetic system, DNAzyme‐loaded manganese‑doped zeolitic imidazolate framework‑90 (ZIF‐90) nanoparticles (ZM@TD) mimic virus nucleocapsid containing genome; erythrocyte membrane mimics viral envelope; two functional peptides, RGD HA2 resemble surface glycoprotein spikes Vir‐ZM@TD can both effectively evade rapid clearance in blood circulation closely serial including specific targeting, fusion‐mediated endosomal escape, TFAM (transcription factor A, mitochondrial) deficiency‐triggered mitochondrial DNA stress, as well release manganese ions (Mn 2+ ) from organelles into cytosol, ultimately priming cGAS‐STING pathway‐mediated with 68% complete regression primary tumors extending 32 days median survival time 4T1‐tumor‐bearing mice.

Language: Английский

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Activation of the cGAS-STING pathway combined with CRISPR-Cas9 gene editing triggering long-term immunotherapy

Biomaterials, Journal Year: 2022, Volume and Issue: 291, P. 121871 - 121871

Published: Oct. 22, 2022

Language: Английский

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Nanoenabled Intracellular Metal Ion Homeostasis Regulation for Tumor Therapy

Advanced Science, Journal Year: 2023, Volume and Issue: 11(7)

Published: Dec. 8, 2023

Abstract Endogenous essential metal ions play an important role in many life processes, especially tumor development and immune response. The approval of various metallodrugs for therapy brings more attention to the antitumor effect ions. With deepening understanding regulation mechanisms ion homeostasis vivo, breaking intracellular becomes a new means inhibit proliferation cells activate Diverse nanomedicines with loading small molecular regulators or have been developed disrupt cells, higher safety efficiency than free compounds. This comprehensive review focuses on latest progress regulation‐based including calcium (Ca 2+ ), ferrous (Fe cuprous (Cu + managanese (Mn zinc (Zn ). physiological functions processes are summarized guide design nanomedicines. Then ions‐based some efficient synergistic therapies highlighted. Finally, challenges future developments also discussed, hoping provide reference finding effective therapies.

Language: Английский

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Lipid‐based nanoparticles as drug delivery systems for cancer immunotherapy

MedComm, Journal Year: 2023, Volume and Issue: 4(4)

Published: Aug. 1, 2023

Abstract Immune checkpoint inhibitors (ICIs) have shown remarkable success in cancer treatment. However, patients without sufficient antitumor immunity, numerous data indicate that blocking the negative signals elicited by immune checkpoints is ineffective. Drugs stimulate activation‐related pathways are emerging as another route for improving immunotherapy. In addition, development of nanotechnology presents a promising platform tissue and cell type‐specific delivery improved uptake immunomodulatory agents, ultimately leading to enhanced immunotherapy reduced side effects. this review, we summarize discuss latest developments nanoparticles (NPs) immuno‐oncology therapy with focus on lipid‐based NPs (lipid‐NPs), including characteristics advantages various types. Using agonists targeting stimulation interferon genes (STING) transmembrane protein an exemplar, review potential lipid‐NPs augment STING agonist therapy. Furthermore, present recent findings underlying mechanisms how pathway activation fosters immunity regulates tumor microenvironment provide summary distinct preclinical studies clinical trials. Ultimately, conduct critical assessment obstacles future directions utilization enhance

Language: Английский

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Manganese(ii) complexes stimulate antitumor immunity via aggravating DNA damage and activating the cGAS-STING pathway

Chemical Science, Journal Year: 2023, Volume and Issue: 14(16), P. 4375 - 4389

Published: Jan. 1, 2023

Activating the cyclic GMP-AMP synthase-stimulator of interferon gene (cGAS-STING) pathway is a promising immunotherapeutic strategy for cancer treatment. Manganese(ii) complexes MnPC and MnPVA (P = 1,10-phenanthroline, C chlorine, VA valproic acid) were found to activate cGAS-STING pathway. The not only damaged DNA, but also inhibited histone deacetylases (HDACs) poly adenosine diphosphate-ribose polymerase (PARP) impede repair DNA damage, thereby promoting leakage fragments into cytoplasm. activated pathway, which initiated an innate immune response two-way communication between tumor cells neighboring cells. further increased production type I interferons secretion pro-inflammatory cytokines (TNF-α IL-6), boosting infiltration dendritic macrophages, as well stimulating cytotoxic T kill in vitro vivo. Owing enhanced DNA-damaging ability, showed more potent immunocompetence antitumor activity than Mn2+ ions, thus demonstrating great potential chemoimmunotherapeutic agents

Language: Английский

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Recent advances in functional bismuth chalcogenide nanomaterials: Cancer theranostics, antibacterial and biosensing

Coordination Chemistry Reviews, Journal Year: 2023, Volume and Issue: 492, P. 215281 - 215281

Published: June 8, 2023

Language: Английский

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