Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
The intractable and devastating nature of pancreatic ductal adenocarcinoma (PDAC) necessitates an urgent need for novel therapies. This study presents the development of a novel polymer prodrug system for the combination treatment of PDAC, based on an optimized pharmacologically active anti-metastatic macromolecular carrier, PCQ, conjugated with gemcitabine (GEM). Structure-activity relationship evaluations showed that random PCQ copolymers exhibited superior anti-migratory activity compared to the gradient PCQ analogs. GEM was incorporated into the random PCQ copolymers using disulfide linker to prepare a reduction-responsive prodrug, PCQ(r)6-SS-GEM12. The resultant therapeutic system presents a pharmacologically active delivery strategy that targets both the proliferative and the metastatic phenotype in PDAC. The PCQ(r)6-SS-GEM12 prodrug demonstrated a selective release of GEM under the reductive tumor environment leading to a significant inhibition of tumor growth with pronounced anti-metastatic effect. Collectively, our data show that the combination of anti-metastatic PCQ and cytotoxic GEM-based reduction-responsive prodrug polymer offers an innovative strategy to treat PDAC.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.biomaterials.2025.123255 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Rac1 palmitoylation is required for cardiac stress adaptation and regulation of Protein Kinase A signaling.
JCI Insight
September 2025
Department of Pharmacology, University of Michigan, Ann Arbor, United States of America.
Cardiac hypertrophy is a common adaptation to cardiovascular stress and often a prelude to heart failure. We examined how S-palmitoylation of the small GTPase, Ras-related C3 botulinum toxin substrate 1 (Rac1), impacts cardiomyocyte stress signaling. Mutation of the cysteine-178 palmitoylation site impaired activation of Rac1 when overexpressed in cardiomyocytes.
View Article and Find Full Text PDFAntithrombin-binding heparan sulfate is ubiquitously expressed in epithelial cells and suppresses pancreatic tumorigenesis.
J Clin Invest
September 2025
Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America.
3-O-sulfation of heparan sulfate (HS) is the key determinant for binding and activation of Antithrombin III (AT). This interaction is the basis of heparin treatment to prevent thrombotic events and excess coagulation. Antithrombin-binding HS (HSAT) is expressed in human tissues, but is thought to be expressed in the subendothelial space, mast cells, and follicular fluid.
View Article and Find Full Text PDFSpontaneous glutamate release activates mGluR signaling to drive rapid antidepressant responses.
Proc Natl Acad Sci U S A
September 2025
Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37240.
Major depressive disorder affects millions worldwide, yet current treatments require prolonged administration. In contrast, ketamine produces rapid antidepressant effects by blocking spontaneous N-Methyl-D-Aspartate (NMDA) receptor signaling, which lifts the suppression of protein synthesis and triggers homeostatic synaptic plasticity. Here, we identify a parallel signaling pathway involving metabotropic glutamate receptor 5 (mGluR5) that promotes rapid antidepressant-like effects.
View Article and Find Full Text PDFPterostilbene as a promising natural anticancer agent in gynecological cancers.
Med Oncol
September 2025
Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
Gynecological cancer, encompassing cancers such as endometrial and cervical cancer, is a growing concern worldwide, with a rising incidence and significant impact on women's health. Pterostilbene (PT), a natural compound, has shown promising therapeutic potential in gynecological cancer treatment. This review aims to summarize the current state of knowledge on PT's effects in gynecological cancer, focusing on its molecular mechanisms, preclinical studies, and clinical trials.
View Article and Find Full Text PDF5-Aminolevulinic acid-mediated photodynamic therapy improves scar healing of laryngeal wounds in rats.
Lasers Med Sci
September 2025
Department of Otolaryngology Head and Neck Surgery, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, 71 Hexi Street, Nanjing 210019, Jiangsu, China.
To evaluated the efficacy of photodynamic therapy (PDT) in improving laryngeal mucosal wound scar healing in vivo and investigated its underlying mechanisms. Laryngeal mucosal wounds were induced in Sprague-Dawley rats. Two weeks post-injury, PDT was administered via intraperitoneal injection of 100 mg/kg 5-aminolevulinic acid (5-ALA) and 635-nm red laser irradiation at varying energy doses (15, 30, and 45 J/cm²).
View Article and Find Full Text PDF