A Dual‐Targeting Biomimetic Nanoplatform Integrates SDT/CDT/Gas Therapy to Boost Synergistic Ferroptosis for Orthotopic Hepatocellular Carcinoma Therapy

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 9, 2025

Abstract The development of efficient therapeutic strategies to promote ferroptotic cell death offers significant potential for hepatocellular carcinoma (HCC) treatment. Herein, this study presents an HCC‐targeted nanoplatform that integrates bimetallic FeMoO 4 nanoparticles with CO‐releasing molecules, and further camouflaged SP94 peptide‐modified macrophage membrane enhanced ferroptosis‐driven multi‐modal therapy HCC. Leveraging the multi‐enzyme activities multivalent metallic elements, not only decomposes H 2 O generate oxygen alleviate tumor hypoxia but also depletes glutathione inactivate peroxides 4, which amplify sonodynamic under ultrasound (US) irradiation. Meanwhile, catalyzes Fenton reaction produce hydroxyl radicals chemodynamic therapy. Elevated intracellular reactive species trigger cascade release CO, leading lethal lipid peroxidation enhancing ferroptosis‐mediated This demonstrates robust anti‐tumor efficacy US irradiation favorable biosafety in both subcutaneous orthotopic HCC models, representing a promising approach Additionally, findings offer new insights into microenvironment modulation optimize US‐triggered cancer

Language: Английский

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Photoredox-Mediated Immunotherapy Utilizing Rhenium(I) Photocatalysts with Electron Donor–Acceptor–Donor Configuration

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 24, 2025

The hypoxic environment of solid tumors significantly diminishes the therapeutic efficacy oxygen-dependent photodynamic therapy. Developing efficient photosensitizers that operate via photoredox catalysis presents a promising strategy to overcome this challenge. Herein, we report rational design two rhenium(I) tricarbonyl complexes (Re-TPO and Re-TP) with electron donor–acceptor–donor configuration. Notably, Re-TP exhibits aggregation-induced emission properties enhanced spin–orbit coupling compared Re-TPO, thus exhibiting promoted photosensitizing capability. In addition generating type I II reactive oxygen species, excited facilitates photocatalytic oxidation NADH NAD+ photoreduction pyruvic acid lactic acid. This metabolic intervention triggers PD-L1-linked immune responses disrupts tumor redox balance, leading ferroptosis immunogenic cell death. combined immunotherapy effects suppress both primary distant B16 tumors. investigation provides compelling model for designing metal-based PSs photoredox-mediated photoimmunotherapy against

Language: Английский

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Self-adaptive photodynamic therapy for boosting therapeutic efficiency in tumor

Science China Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

Language: Английский

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Endoplasmic Reticulum-Targeted Phototherapy Remodels the Tumor Immunopeptidome to Enhance Immunogenic Cell Death and Adaptive Anti-Tumor Immunity

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(4), P. 491 - 491

Published: March 28, 2025

Background: Endoplasmic reticulum (ER)-targeted phototherapy has emerged as a promising approach to amplify ER stress, induce immunogenic cell death (ICD), and enhance anti-tumor immunity. However, its impact on the antigenicity of dying tumor cells remains poorly understood. Methods: Laser activation ER-targeted photosensitizer ER-Cy-poNO2 was performed investigate effects antigenicity. Transcriptomic analysis carried out assess gene expression changes. Immunopeptidomics profiling used identify high-affinity major histocompatibility complex class I (MHC-I) ligands. In vitro functional studies were conducted evaluate dendritic maturation T lymphocyte activation, while in vivo experiments by combining identified peptide with poly IC Results: significantly remodeled antigenic landscape 4T-1 cells, enhancing their immunogenicity. revealed upregulation antigen processing presentation pathways. multiple MHC-I ligands, IF4G3986–994 (QGPKTIEQI) showing exceptional vitro, promoted enhanced lymphocytes activation. vivo, combination elicited robust immunity, characterized increased CD8+ infiltration, reduced regulatory (Tregs) microenvironment, elevated systemic Interferon-gamma (IFN-γ) levels, significant growth inhibition without toxicity. Conclusions: These findings establish mechanistic link between stress-driven ICD, immunopeptidome remodeling, adaptive immune highlighting potential platform for identifying peptides advancing peptide-based cancer vaccines.

Language: Английский

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Photochemical bomb: Precision nuclear targeting to activate cGAS-STING pathway for enhanced bladder cancer immunotherapy

Biomaterials, Journal Year: 2025, Volume and Issue: unknown, P. 123126 - 123126

Published: Jan. 1, 2025

Language: Английский

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A photo-accelerated nanoplatform for image-guided synergistic chemo-photodynamic therapy

Chinese Chemical Letters, Journal Year: 2025, Volume and Issue: unknown, P. 110942 - 110942

Published: Feb. 1, 2025

Language: Английский

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Spheroid‐on‐a‐Chip Platforms for Tumor Microenvironment and Drug Development

Advanced Materials Technologies, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 12, 2025

Abstract Despite significant advancements in oncology research and therapeutic interventions, cancer continues to be the leading cause of mortality worldwide. The key challenge addressing this pressing issue lies lack precision diagnosis a limited understanding nature how tumor microenvironment responds interventions. Research focusing on impact (TME) heterogeneity response drugs is crucial ensure efficient therapy. Conventional models exhibit constraints, including inability accurately imitate tumors’ complex 3D architecture dynamic microenvironment. Recent developments Spheroid‐On‐a‐Chip (SoC) technology provide alternative, offering closer that human tissue. This review explores recent SoC modeling, highlighting spheroid formation mechanisms techniques. applications platform mimic essential features their potential role anticancer drug development are summarized. advantages challenges technologies behind devices compared traditional vitro further discussed. Lastly, future directions for transforming improving suggested.

Language: Английский

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Pyrrolopyrrole Cyanine-Based Polymer with Superior Multifunctionality for Boosting Cancer Phototheranostics

ACS Materials Letters, Journal Year: 2025, Volume and Issue: unknown, P. 1431 - 1439

Published: March 19, 2025

Molecular agents with exceptional multifunctionality are highly sought for phototheranostic applications. Herein we present a high-performance polymer near-infrared II (NIR-II) fluorescence and photoacoustic (PA) imaging-guided mild photothermal therapy (mPTT) of tumors. We synthesize series semiconducting polymers based on pyrrolopyrrole cyanine, identifying that P(P-T) exhibits large mass extinction coefficient (139 L g–1 cm–1), excellent performance, bright NIR-II fluorescence, PA imaging signals, making it among the highest-performing in these properties. A tumor-targeting agent was developed by coencapsulating heat shock protein (HSP) inhibitor camouflaging M1 macrophage membranes. The integration enables comprehensive tumor site delineation, guiding subsequent therapeutic intervention. In 4T1 tumor-bearing mice, synergistic effect mPTT under low-power 808 nm laser irradiation, combined HSP inhibition, resulted significant suppression. This work offers valuable insights designing advanced agents.

Language: Английский

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Ultrasound-Energized OX40L-Expressing Biohybrid for Multidimensional Mobilization of Sustained T Cell-Mediated Antitumor Immunity and Potent Sono-Immunotherapy

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: April 9, 2025

Harnessing immunostimulation to reinvigorate antitumor effector immune cells represents a promising strategy for tumor eradication. However, achieving durable clinical outcomes necessitates multidimensional activation sustain robust responses. Here, we present an ultrasound-empowered living biohybrid that strategically mobilizes T-cell-mediated immunity potent sono-immunotherapy. Through synthetic biology, engineer bacteria express fusion protein encoding the costimulatory OX40 ligand (OX40L), and further functionalize them with high-performance polymer sonosensitizer tethered via reactive oxygen species-cleavable linker. Upon ultrasound irradiation, sono-activated nanocargoes detach from bacterial surface, facilitating cellular entry exposing immune-stimulating OX40L. The sonodynamic effects, coupled native immunogenicity of bacteria, promotes tumor-associated antigen release, fosters proinflammatory microenvironment, drives dendritic cell maturation, thereby priming cytotoxic T-cell activation. OX40L expressed by engineered amplifies sustains activity, orchestrating response. This cascade-amplified effectively suppresses growth, induces long-lasting memory, provides protection against metastasis recurrence, significantly enhancing survival outcomes. By integrating ultrasound-energized nanoadjuvants boosters, this hybrid biotherapeutic platform offers versatile powerful activation, advancing frontier cancer

Language: Английский

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Endogenous Nanoplatforms for Tumor Photoimmunotherapy: Hypoxia Modulation and STING Pathway Activation

Acta Biomaterialia, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

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