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

Self-Reporting Ratiometric AIEgen-Peptide Nanoprobes for Activatable Chemotherapy and Noninvasive Imaging of Therapeutic Outcomes

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

Published: April 2, 2025

Efficacious chemotherapy and real-time therapeutic monitoring remain major challenges in cancer treatment. Traditional systems often lack tumor specificity, limiting efficacy, hindering therapy optimization. Moreover, the absence of can lead to missed opportunities increased risks side effects. Herein, we designed a self-reporting ratiometric AIEgen-peptide nanoprobe (TPE-1(Hyd-DOX)-DEVD) for activatable noninvasive imaging outcomes. When doxorubicin (DOX) is selectively activated acidic microenvironment, ensuing caspase-3 cascade triggers morphological transformation that amplifies TPE fluorescence. This enhancement allows TPE/DOX fluorescence ratio serve as an indicator DOX activation providing feedback. Both vitro vivo studies demonstrated TPE-1(Hyd-DOX)-DEVD exhibited impressive suppression efficacy excellent biocompatibility. study highlights strong potential this valuable tool theranostics, offering hope more effective personalized treatment strategies.

Language: Английский

Photothermal Amplification of Calcium Ion Overload for Tumor Homing Therapy

ACS Materials Letters, Journal Year: 2025, Volume and Issue: unknown, P. 2319 - 2327

Published: May 21, 2025

Language: Английский