Gracilaria edulis-mediated silver nanoparticles as a targeted strategy for cervical cancer with integrated toxicity...

Cervical cancer remains a critical global health concern, demanding the development of innovative therapies to address the limitations of conventional chemotherapeutics, including systemic toxicity and lack of specificity. Silver nanoparticles synthesized using Gracilaria edulis (GE-AgNPs) present a novel therapeutic strategy, exhibiting selective cytotoxicity against the HEK293 normal epithelial cell line and HeLa cervical cancer cell line. Phytochemical analysis of Gracilaria edulis identified bioactive compounds such as 4-Benzaldehyde and 1H-1,3-Benzimidazole-1-acetonitrile, both associated with potent anticancer activities. Comprehensive characterization of GE-AgNPs through spectroscopy and microscopy revealed distinctive physicochemical properties, including an absorption peak at 332 nm and a hexagonal crystalline structure. Cytotoxicity assays confirmed that GE-AgNPs induce apoptosis in HeLa cells exhibit a concentration-dependent response, with an IC₅₀ value of 54.05 μg/mL, while GE-AgNPs exhibited no significant toxicity to HEK293 cells at the tested concentrations, as evidenced by a higher IC₅₀ value of 83.6 μg/mL. The pro-apoptotic effect was mediated through the development of reactive oxygen species (ROS), validated using dual staining and Hoechst assays, which demonstrated chromatin condensation indicative of apoptosis. Molecular analysis further elucidated the mechanism of action, highlighting significant inhibition of the PI3K/AKT signaling pathway. This was evidenced by downregulation of PI3K, AKT, and mTOR genes alongside the upregulation of PTEN, a critical tumor suppressor. Zebrafish embryo toxicity assays provided insights into the biocompatibility of GE-AgNPs, revealing low toxicity at therapeutic concentrations but developmental abnormalities and neurotoxicity at higher doses. These findings underscore the promise of GE-AgNPs as a targeted therapy option for cervical cancer, effectively modulating the PI3K/AKT pathway while maintaining manageable toxicity profiles. Further investigations into optimizing dosing regimens and exploring synergistic effects with existing treatments could enhance their clinical applicability.