The assembly modules deformation strategy improved the chemical stability and self-assembly stability of docetaxel prodrugs nanoassemblies

Nanoscale, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Self-assembly prodrugs usually consist of drug modules, activation and assembly modules. The selection suitable modules to construct prodrug nanoassemblies with self-assembly stability "intelligent" is a challenge. As common module, oleic acid can provide driving force steric hindrance for self-assembly. However, the unsaturated double bond readily oxidized it affects its chemical stability. Herein, two docetaxel (DTX) were designed using disulfide bonds as different fatty acids (isostearic acid) respectively. Compared acid, isostearic had higher Simultaneously, terminal propyl structure compensated without bond. Overall, this structural deformation improved ability nanoassemblies, thus balancing effectiveness safety prodrugs. Our findings reveal importance guidance rational design nanoassemblies.

Language: Английский

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Design, Synthesis, and Biological Evaluation of BODIPY-Caged Resiquimod as a Dual-Acting Phototherapeutic

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

Published: Feb. 17, 2025

Resiquimod, an imidazoquinoline scaffold, exhibits potent immunotherapeutic activity but is associated with off-target effects, limiting its clinical utility. To address this limitation, we developed a novel BODIPY-caged resiquimod that responsive to red light, combining photocaging and photodynamic therapy functionalities. Molecular docking studies guided identification of the optimal caging site for resiquimod, effectively masking immune activity. remained inactive under dark conditions, resiquimod's immunostimulatory effects. However, light irradiation precisely uncaged inducing robust activation, even in presence N-acetyl cysteine as antioxidant. Notably, attachment BODIPY reduced toxicity typically photosensitizer. In 3D spheroid models HeLa A549 cells, demonstrated spatiotemporal control over cytotoxicity, significantly enhancing cell death only upon irradiation. This dual-function therapeutic approach highlights "win–win" strategy: precise, red-light-mediated activation efficacy collateral toxicity.

Language: Английский

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Restoring Tumor Cell Immunogenicity Through Ion‐Assisted p53 mRNA Domestication for Enhanced In Situ Cancer Vaccination Effect

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

Published: Feb. 18, 2025

Abstract The efficacy of in situ cancer vaccines (ISCVs) is hindered by the poor immunogenicity tumor cells. Here, PRIZE, a P53‐repair nanosystem based on virus‐mimicking nanostructure to deliver p53 mRNA and Zn (II) into cells, domesticating cells restoring intracellular P53 levels bolster their immunogenicity, designed. PRIZE ensures precise delivery sites, stabilizes with its biomineralized structure, extends half‐life P53. This research highlights that can efficiently repair abnormalities 4T1 (P53‐deficient) MC38 (P53‐mutant) subsequently upregulating expression major histocompatibility complex (MHC) class I molecules surface co‐stimulatory molecule CD80 enhancing antigen presentation transforming reservoirs. co‐delivered photothermal agent (ICG) trigger immunogenic cell death under laser irradiation, effectively releasing tumor‐associated antigens, inducing formation ISCVs. Importantly, abnormal mouse models, induced ISCVs initiate immune cycle (CIC), demonstrating outstanding tumoricidal immunity thwarting metastasis postoperative recurrence, which provides valuable insights for advancing personalized immunotherapy.

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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Alkaline phosphatase-responsive lipid-like polyphosphonitrile nanovesicles to enhance immunotherapy and inhibit metastasis of triple-negative breast cancer

Chemical Engineering Journal, Journal Year: 2025, Volume and Issue: unknown, P. 163576 - 163576

Published: May 1, 2025

Language: Английский

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