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Improving the Anti-Tumor Effect of Indoleamine 2,3-Dioxygenase Inhibitor CY1-4 by CY1-4 Nano-Skeleton Drug Delivery System.
J Funct Biomater
December 2024
Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
CY1-4, 9-nitropyridine [2',3':4,5] pyrimido [1,2-α] indole -5,11- dione, is an indoleamine 2,3-dioxygenase (IDO) inhibitor and a poorly water-soluble substance. It is very important to increase the solubility of CY1-4 to improve its bioavailability and therapeutic effect. In this study, the mesoporous silica nano-skeleton carrier material Sylysia was selected as the carrier to load CY1-4, and then the CY1-4 nano-skeleton drug delivery system (MSNM@CY1-4) was prepared by coating the hydrophilic polymer material Hydroxypropyl methylcellulose (HPMC) and the lipid material Distearoylphosphatidyl-ethanolamine-poly(ethylene glycol) (DSPE-PEG) to improve the anti-tumor effect of CY1-4.
View Article and Find Full Text PDFEngineering Modular Peptide Nanoparticles for Ferroptosis-Enhanced Tumor Immunotherapy.
Angew Chem Int Ed Engl
December 2024
Westlake University, Chemistry, 18 Shilongshan Road, 310024, Hangzhou, CHINA.
Indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors are promising for treating tumors but have limited efficacy due to the immunosuppressive tumor microenvironment. In this study, we develop an orchestrated nanoparticle system using modular peptide assemblies, where the co-assembled sequences are designed for the specific binding to the hydrophobic and hydrophilic domains, guiding the assembly process and enabling the customization of nanoparticle properties. We exploit the modularity of this platform to integrate a hydrophobic ferroptosis precursor, an IDO1 inhibitor, and a hydrophilic peptidic PD-L1 antagonist for optimizing therapeutic outcomes through ferroptosis-enhanced tumor immunotherapy.
View Article and Find Full Text PDFPyruvate Kinase M2-Responsive Release of Paclitaxel and Indoleamine 2,3-Dioxygenase Inhibitor for Immuno-Chemotherapy of Nonsmall Cell Lung Cancer.
Adv Sci (Weinh)
December 2024
Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China.
Paclitaxel (PTX) is a first-line chemotherapeutic drug for non-small cell lung cancer (NSCLC) but it can induce indoleamine 2,3-dioxygenase (IDO) activation, which severely lowers down its immuno-chemotherapeutic effect. To address this issue, a smart peptide hydrogelator Nap-Phe-Phe-Phe-Lys-Ser-Thr-Gly-Gly-Lys-Ala-Pro-Arg-OH (Nap-T), which co-assembles with PTX and an IDO inhibitor GDC0919 to form a hydrogel GP@Gel Nap-T, is rationally designed. Upon specific phosphorylation by pyruvate kinase M2 (PKM2), an overexpressed biomarker of NSCLC, Nap-T is gradually converted to Nap-Phe-Phe-Phe-Lys-Ser-Thr(HPO)-Gly-Gly-Lys-Ala-Pro-Arg-OH (Nap-Tp), leading to dehydrogelation and sustained release of PTX and GDC0919 within NSCLC tissues.
View Article and Find Full Text PDFSynthesis and Activity Study of Gefitinib Derivatives Inducing Mitochondrial Apoptosis in Hela Cells.
Chem Biol Drug Des
December 2024
College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, Luoyang, Henan, China.
Cervical cancer is the fourth most common cancer among women globally. Its development is closely linked to accelerated cell cycle progression and the inhibition of apoptosis in cervical cancer tissues. Gefitinib has demonstrated efficacy in inhibiting cervical cancer cells, and the 1,2,3-triazole structure is widely recognized for its role in inducing mitochondrial apoptosis in tumor cells.
View Article and Find Full Text PDFCannabidiol Suppresses Metastatic Castration-Resistant Prostate Cancer Progression and Recurrence through Modulating Tryptophan Catabolism.
ACS Pharmacol Transl Sci
December 2024
School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Drive, Monroe, Louisiana 71201, United States.
Metastatic castration-resistant prostate cancer (mCRPC) is an aggressive phenotype of prostate cancer (PC). Tryptophan oxidative catabolism by indoleamine 2,3-dioxygenase-1 (IDO1) cleaves the indole ring to kynurenine (Kyn), an endogenous ligand for the aryl hydrocarbon receptor (AhR), which activates multiple tumorigenesis pathways. The IDO1-Kyn-AhR axis is aberrantly dysregulated in mCRPC.
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