Interrelation between Programmed Cell Death and Immunogenic Cell Death: Take Antitumor Nanodrug as an Example

Small Methods, Journal Year: 2023, Volume and Issue: 7(5)

Published: Jan. 27, 2023

Abstract Programmed cell death (PCD, mainly including apoptosis, necrosis, ferroptosis, pyroptosis, and autophagy) immunogenic (ICD), as important mechanisms, are widely reported in cancer therapy, understanding the relationship between two is significant for clinical tumor treatments. Considering that vast nanodrugs developed to induce PCD ICD simultaneously, this review, interrelationship described using nanomedicines examples. First, an overview of patterns focus on morphological differences interconnections among them provided. Then apoptosis terms endoplasmic reticulum stress by introducing various treatments recent developments with inducible immunogenicity. Next, crosstalk non‐apoptotic (including signaling pathways introduced their through examples further illustrated. Finally, its application prospects development new nanomaterials summarized. This review believed deepen ICD, extend biomedical applications nanodrugs, promote progress therapy.

Language: Английский

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Simultaneous Activation of Pyroptosis and cGAS‐STING Pathway with Epigenetic/ Photodynamic Nanotheranostic for Enhanced Tumor Photoimmunotherapy

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(7)

Published: Oct. 5, 2023

Promoting innate immunity through pyroptosis induction or the cyclic GMP-AMP synthase-stimulator of interferon gene (cGAS-STING) pathway activation has emerged as a potent approach to counteract immunosuppressive tumor microenvironment and elicit systemic antitumor immunity. However, current inducers STING agonists often suffer from limitations including instability, unpredictable side effects, inadequate intracellular expression gasdermin STING. Here, tumor-specific nanotheranostic platform that combines photodynamic therapy (PDT) with epigenetic simultaneously activate cGAS-STING in light-controlled manner is constructed. This involves development oxidation-sensitive nanoparticles (NP1) loaded photosensitizer TBE, along decitabine nanomicelles (NP2). NP2 enables restoration E (GSDME) expression, while NP1-mediated PDT facilitates release DNA fragments damaged mitochondria potentiate pathway, promotes caspase-3 cleave upregulated GSDME into pore-forming GSDME-N terminal. Subsequently, released inflammatory cytokines facilitate maturation antigen-presentation cells, triggering T cell-mediated Overall, this study presents an elaborate strategy for simultaneous photoactivation enabling targeted photoimmunotherapy immunotolerant tumors. innovative holds significant promise overcoming associated existing therapeutic modalities represents valuable avenue future clinical applications.

Language: Английский

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A STING pathway-activatable contrast agent for MRI-guided tumor immunoferroptosis synergistic therapy

Biomaterials, Journal Year: 2023, Volume and Issue: 302, P. 122300 - 122300

Published: Aug. 29, 2023

Language: Английский

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A Vanadium-Based Nanoplatform Synergizing Ferroptotic-like Therapy with Glucose Metabolism Intervention for Enhanced Cancer Cell Death and Antitumor Immunity

ACS Nano, Journal Year: 2023, Volume and Issue: 17(12), P. 11537 - 11556

Published: June 5, 2023

Ferroptosis activation has been considered a mighty weapon for cancer treatment, and growing attention is being paid to reinforcing tumor cells' sensitivity ferroptosis. However, the existence of certain ferroptosis resistance mechanisms, especially abnormal metabolism cells, long underestimated. We propose an enhanced ferroptosis-activating pattern via regulating glycometabolism construct nanoplatform named PMVL, which composed lonidamine (LND)-loaded tannic acid coordinated vanadium oxides with camouflage PD-L1 inhibiting peptide-modified cell membrane. This work reveals that mixed valence (VIV VV) in PMVL triggers due self-cyclic alteration V, process generates •OH lipid peroxide accumulation → depletes glutathione (GSH) peroxidase (GPX4) deactivation (VV VIV). Notably, LND strengthens by dual suppression glycolysis (decreasing ATP supply) pentose phosphate pathway NADPH production), causing anabatic GSH consumption. Besides, inhibited less intracellular lactic alleviates acidity microenvironment, preventing immunosuppressive M2 macrophage polarization. In vitro vivo data demonstrate glycometabolism-intervention-enhanced boosted immunity activation, potentially providing opportunities possibilities synergetic therapy.

Language: Английский

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Mitochondrial Localized In Situ Self‐Assembly Reprogramming Tumor Immune and Metabolic Microenvironment for Enhanced Cancer Therapy

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(15)

Published: Jan. 8, 2024

Abstract The inherent immune and metabolic tumor microenvironment (TME) of most solid tumors adversely affect the antitumor efficacy various treatments, which is an urgent issue to be solved in clinical cancer therapy. In this study, a mitochondrial localized situ self‐assembly system constructed remodel TME by improving immunogenicity disrupting plasticity cells. peptide‐based drug delivery can pre‐assembled into nanomicelles vitro form functional nanofibers on mitochondria through cascade‐responsive process involving reductive release, targeted enrichment, self‐assembly. organelle‐specific self‐assemblyeffectively switches role mitophagy from pro‐survival pro‐death, finally induces intense endoplasmic reticulum stress atypical type II immunogenic cell death. Disintegration ultrastructure also impedes cells, greatly promotes immunosuppresive remodeling immunostimulatory TME. Ultimately, effectively suppresses metastases, converts cold hot with enhanced sensitivity radiotherapy checkpoint blockade This study offers universal strategy for spatiotemporally controlling supramolecular sub‐organelles determine fate enhance

Language: Английский

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