Dual antimicrobial and anticancer functions of artemisinin-loaded PEG400-oa nanoparticles: synergistic activity with ciprofloxacin and mechanistic insights from molecular docking

Artemisinin, a bioactive compound from Artemisia annua with potent antioxidant, antimicrobial and anticancer properties, faces limited clinical utility due to poor solubility and low bioavailability. Given the rising prevalence of multidrug-resistant (MDR) Pseudomonas aeruginosa alternative therapeutic strategies are essential. This study synthesized and characterized artemisinin-loaded micelle/liposome nanoparticles (Art/PEG 400 -OA NPs) and evaluated their antibacterial, antibiofilm, and anticancer efficacy. Artemisinin was successfully encapsulated within PEG 400 -OA NPs and characterized via FT-IR, FE-SEM, TEM, TGA, and zeta potential measurements. The nanoparticles exhibited uniform morphology, particle sizes of 40.8 nm (TEM) and 149.8 nm (FE-SEM), high encapsulation efficiency (92.14%), and strong thermal and colloidal stability. Synergistic and partial synergistic interactions between Art/PEG 400 -OA NPs and ciprofloxacin were observed in MDR bacterial samples, significantly inhibiting biofilm formation. Quantitative RT-PCR analysis revealed the downregulation of efflux pump genes ( mexA , mexB , mexX , mexY , oprM ) and biofilm-associated genes ( algD , pelA ) following combination therapy. In AGS gastric cancer cells, Art/PEG 400 -OA NPs induced dose- and time-dependent cytotoxicity (IC₅₀: 67.75, 62.25 and 54.98 µg/mL at 24, 48 and 72 h), increased apoptosis (31.76% ± 4.2%), and reduced wound-healing migration (56.65% ± 4.26%). Expression analysis demonstrated upregulation of tumor-suppressive miR-34a, and downregulation of its targets ( CTNNB1 , TGFB1 , MMP2 and MMP9 ). Conversely, miR-181a was downregulated, leading to the upregulation of apoptotic target genes ( TP53 , CASP8 , CASP9 ). Molecular docking supported strong artemisinin binding to key bacterial and oncogenic proteins. Overall, Art/PEG 400 -OA nanoparticles represent a potent dual-action nanotherapeutic platform against antibiotic-resistant infections and gastric cancer.