Akademik Veri Yönetim Sistemi
Journal of Drug Delivery Science and Technology, cilt.111, 2025 (SCI-Expanded)
Metal-organic frameworks (MOFs) show promise for anticancer drug delivery. This study investigates the efficacy of strontium (Sr)-based MOFs for delivering methotrexate (MTX, folate analog) to folate receptor (FR)-positive U-87MG/glioblastoma and HeLa/cervical-carcinoma cells and spheroids. Herein, Sr-based MOFs with terephthalic acid (BDC) were synthesized via flow-controlled solvothermal synthesis to generate MTX-loaded nanoparticles (NPs) for the first time. SEM, TEM, DLS, DSC, and FTIR analyses revealed that NPs had three-dimensional structure, nanoscale particle size (∼100 nm), narrow size distribution, and good stability. Confocal microscopy confirmed their penetration into U-87MG glioblastoma and HeLa cervical-carcinoma cell monolayers and spheroids. MTT results (treatment-time:1-h, analysis at 48-h and 72-h) showed that bound-MTX was more effective at lower doses than free-MTX, with increased drug sensitivity (3.72 and 15.94 for U-87MG, 6.25 and 31.25 for HeLa cells, respectively). MTX/Sr-BDC MOFs had negligible penetration into FR− HEK-293 normal cells and low toxicity. Remarkably, MTX/Sr-BDC MOFs (treatment-dose/time: 2.5 μg/mL MTX/1-h, analysis at 48-h) significantly downregulated inflammation (decreased NF-κB-p65, IL-1β, IL-6, TNF-α, and increased IL-10 levels)/epithelial-mesenchymal transition (EMT; decreased N-cadherin/E-cadherin ratio and Snail, Twist1, TGF-β levels) axis, reduced migration/colony-formation ability, and induced apoptosis. Moreover, tumor growth in 3D-spheroids (mimicking in vivo tumors) treated with MTX/Sr-BDC MOFs was observed to slow down significantly based on dose (2.5–25 μg/mL) and time (2 and 7-days), with reduced viability compared to untreated or free-drug groups. These outputs indicate that Sr-based MOFs could serve as a delivery system for MTX in treating aggressive glioblastoma and cervical tumors by targeting the inflammation-EMT axis and inducing apoptosis.