Biomaterials, Год журнала: 2024, Номер 316, С. 122998 - 122998
Опубликована: Дек. 9, 2024
Язык: Английский
International Journal of Nanomedicine, Год журнала: 2025, Номер Volume 20, С. 181 - 197
Опубликована: Янв. 1, 2025
Abstract: The microenvironment tends to be immunosuppressive during tumor growth and proliferation. Immunotherapy has attracted much attention because of its ability activate tumor-specific immune responses for killing. cyclic GMP-AMP synthase-stimulator interferon genes (cGAS-STING) pathway is an innate that activates antitumor immunity by producing type I interferons. Cyclic dinucleotides (CDNs), produced cGAS sensing cytoplasmic abnormal DNA, are major intermediate activating molecules in the STING pathway. Nowadays, CDNs their derivatives have widely worked as powerful agonists immunotherapy. However, clinical translation hindered negative electrical properties, sensitivity hydrolytic enzymes, systemic toxicity. Recently, various CDN delivery systems made significant progress addressing these issues, either through monotherapy or combination with other treatment modalities. This review details recent advances CDNs-based pharmaceutical development strategies enriching at sites Keywords: dinucleotides, stimulator pathway, immunotherapy
Язык: Английский
Процитировано
0
Advanced Healthcare Materials, Год журнала: 2025, Номер unknown
Опубликована: Янв. 15, 2025
Myocarditis, a leading cause of sudden cardiac death and heart transplantation, poses significant treatment challenges. The study clinical samples from myocarditis patients reveals correlation between the pathogenesis cardiomyocyte mitochondrial DNA (mtDNA). During inflammation, concentration mtDNA in cardiomyocytes increases. Hence, it is hypothesized that combined clearance its downstream STING pathway can treat myocarditis. However, clearing problematic. An innovative scavenger introduced, Nanosweeper (NS), which utilizes nanostructure to facilitate transport NS-mtDNA co-assemblies for degradation, achieving clearance. fluorescent probe on NS, bound functional peptides, enhances stability NS. NS also exhibits robust human plasma with half-life up 10 hours. In murine model, serves as drug delivery vehicle, targeting inhibitor C-176 myocardium. This approach synergistically modulates cGAS-STING axis effectively attenuating myocarditis- associated inflammatory cascade. evaluation porcine models corroborated superior biosafety profile capability. strategic targeted couple inhibition, significantly augments therapeutic efficacy against myocarditis, outperforming conventional C-176, indicating potential.
Язык: Английский
Процитировано
0
International Immunopharmacology, Год журнала: 2025, Номер 148, С. 114013 - 114013
Опубликована: Янв. 18, 2025
Язык: Английский
Процитировано
0
Biomaterials, Год журнала: 2025, Номер 318, С. 123170 - 123170
Опубликована: Фев. 5, 2025
Язык: Английский
Процитировано
0
Journal of Controlled Release, Год журнала: 2025, Номер unknown
Опубликована: Фев. 1, 2025
Язык: Английский
Процитировано
0
Journal of Controlled Release, Год журнала: 2025, Номер unknown
Опубликована: Фев. 1, 2025
Язык: Английский
Процитировано
0
IUBMB Life, Год журнала: 2025, Номер 77(3)
Опубликована: Март 1, 2025
The cGAS-STING signaling pathway has emerged as a critical player in the immune response against cancer, including colorectal adenocarcinoma (COAD). Understanding impact of this on COAD at multiple omics levels is crucial for advancing cancer immunotherapy and precision medicine. This study aimed to investigate relationship between cGAS-STING-related genes COAD, analyzing gene mutations, copy number variations, DNA methylation, expression uncover pathway's influence prognosis. Utilizing multi-omics sequencing data from TCGA GEO databases, key core were identified further validated through PCR Western blot analysis. Mutations variations CASP8 RIPK1 genes, differential methylation patterns, mRNA specific assessed determine their Validation tissue samples highlighted NLRC3, CASP1, AIM2, CXCL10 pathway. Our findings demonstrate that mutations RIPK1, altered significantly prognosis COAD. identification pathway, particularly CXCL10, led development prognostic model predicting poor tumor outcomes cell infiltration. provides valuable insights into mechanisms offers potential directions future research
Язык: Английский
Процитировано
0
Journal of Colloid and Interface Science, Год журнала: 2025, Номер 690, С. 137326 - 137326
Опубликована: Март 15, 2025
Язык: Английский
Процитировано
0
Frontiers in Pharmacology, Год журнала: 2025, Номер 16
Опубликована: Апрель 8, 2025
Introduction Osteosarcoma (OS) is the most common primary malignant bone tumor in pediatric populations. Its treatment complicated by chemotherapy-induced toxicity and limited induction of immunogenic cell death (ICD). Methods To address these challenges, we developed a pH-responsive, multi-component nanoparticle system designed to co-deliver doxorubicin (DOX), monophosphoryl lipid A (MPLA), PD-1/PD-L1-targeting peptide, integrated with immune-modulating polymer PEG-PC7A. The was optimized using both one-factor-at-a-time (OFAT) Box-Behnken design (BBD). Results nanoparticles had hydrodynamic size 110 nm, high encapsulation efficiency (97.15%), pH-sensitive drug release (91% at pH 6.5). In vitro studies showed enhanced ICD markers, including calreticulin exposure ATP/HMGB1 release, aswell as synergistic dendritic maturation via dual STING/TLR4 pathway activation. an orthotopic LM8 osteosarcoma model, significantly suppressed growth, promoted cytotoxic T lymphocyte infiltration, reduced regulatory cells, established long-term immune memory. Discussion combination induction, innate activation, checkpoint blockade reprogrammed microenvironment, amplifying anti-tumor responses. These results demonstrate potential this multifunctional platform effective immunochemotherapeutic strategy for osteosarcoma, offering therapeutic efficacy systemic toxicity.
Язык: Английский
Процитировано
0
Medical Oncology, Год журнала: 2025, Номер 42(5)
Опубликована: Апрель 12, 2025
Язык: Английский
Процитировано
0