Speaker
Description
Glory Kah and Heidi Abrahmse*
Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, Doornfontein Campus. Post Office Box 17011, Johannesburg 2028, South Africa
*Correspondence: Heidi Abrahamse. Email: habrahamse@uj.ac.za
Abstract. Lung cancer remains a leading cause of cancer-related mortality worldwide, largely due to therapeutic resistance mediated by lung cancer stem cells (LCSCs). This study aimed to develop and evaluate a bioformulated curcumin–silver nanoparticle conjugate (Cum-PEG-BpAgNPs) for enhanced photodynamic therapy (PDT) targeting both lung cancer cells (A549) and their stem cell subpopulations. Silver nanoparticles were synthesized using Bidens pilosa extract and conjugated with curcumin to form the nanoconjugate, which was subsequently characterized. LCSCs expressing CD133⁺ and CD44⁺ markers were isolated via immunomagnetic bead sorting and confirmed by immunofluorescence. Cellular uptake and subcellular localization were assessed using fluorescence microscopy. Cytotoxicity following dark and 470 nm laser irradiation (5 J/cm²) was evaluated using MTT, LDH, and ATP assays, while reactive oxygen species (ROS) generation, mitochondrial membrane potential disruption, apoptosis–necrosis profiling, and expression of apoptosis-related proteins (p53, caspase-3, and Bcl-2) were analyzed using DCFH-DA, JC-10, Annexin V-FITC/PI, and ELISA assays, respectively. Cum-PEG-BpAgNPs-mediated PDT demonstrated significantly greater cytotoxicity compared to free curcumin, with lower IC₅₀ values in both A549 cells (4.01 µg/mL) and LCSCs (2.37 µg/mL). Enhanced intracellular uptake and broad organelle co-localization were observed for the nanoconjugate. Treatment induced elevated ROS production, mitochondrial dysfunction, and predominantly apoptotic cell death, characterized by upregulation of p53 and caspase-3 and downregulation of Bcl-2. In conclusion, the Cum-PEG-BpAgNPs nanoconjugate significantly improves PDT efficacy against lung cancer cells and resistant LCSCs by promoting ROS-mediated mitochondrial apoptosis, highlighting its potential as a therapeutic strategy for resistant lung cancer.
