Folate-directed morin nano-gold decorated with chitosan: a multifunctional arsenal against triple-negative breast cancer and AMR superbugs.

TNBC defying conventional therapies and the rapid increase in antimicrobial resistance disarming powerful antibiotics demand urgent clinical intervention. The current research study explored a strategy to target TNBC and drug-resistant pathogens using flavonoid (morin)-induced gold nanoparticles (MorAunps) tethered with folic acid and chitosan (CH/FA-MorAunps) for enabling targeting approach and induced cellular uptake. The synthesized nanosystems with a size of 21.87 nm exhibited a spherical morphology with utmost stability. The synthesized nanoformulations were assessed for in vitro antioxidant, antimicrobial and anticancer activity. The CH/FA-MorAunps were found to be excellent antioxidants with scavenging capacity ranging from 83% to 96%. The tagging of chitosan also dramatically enhanced the antimicrobial potency (MIC ranging from 8 to 32 µg mL-1), outperforming standard's MICs. The nanosystems exhibited significant cytotoxicity against both BC and TNBC cells (IC50 values of 4.29 and 8.32 µg mL-1, respectively). The enhanced anticancer potential of the nanosystems was most likely driven by rapid internalization, G2/M phase cell cycle arrest, and ROS-mediated apoptotic and necrotic deaths, as evidenced in MDA-MB-231 cells. In addition, the nanoparticles did not confer significant toxicity against non-malignant cells, reinforcing their biosafety and translational viability. Further docking analysis of the flavonoid with potential cancer, microbial and oxidative stress-related targets revealed significant docking scores in the range of 7-9 kcal mol-1 and specific interactions with active pockets, providing a strong mechanistic view of the nanosystems as a multifaceted bioactive nanoplatform. This pioneering study establishes morin-conjugated gold nanoparticles as a powerful targeted nanotherapeutic platform against triple-negative breast cancer and AMR pathogens.