Eco-Friendly Selenium-Hyaluronic Acid Nanoconjugates with Potent Anticancer, Antimicrobial, Anti-Inflammatory and Wound-Healing Activities.

Cancer and multidrug-resistant microbial infections remain major global health challenges, underscoring the need for multifunctional, biocompatible, and environmentally sustainable therapeutic platforms. Herein, selenium-hyaluronic acid nanoconjugates (Se/HA NPs) were synthesized through an eco-friendly ascorbic acid-mediated reduction approach to improve the bio-functional stability and therapeutic performance of selenium-based nanomaterials. The formation of Se/HA NPs was confirmed by transmission electron microscopy (TEM), X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDX), and Fourier-transform infrared spectroscopy (FTIR). FTIR analysis supported the involvement of ascorbic acid- and hyaluronic acid-associated functional groups in nanoparticle formation and stabilization. TEM revealed well-dispersed, predominantly spherical nanoparticles with diameters ranging from 29.72 to 80.38 nm, while XRD confirmed their crystalline nature with an average crystallite size of 31.2 nm. Biologically, Se/HA NPs exhibited strong antibacterial activity against Enterococcus faecalis (21 mm), Staphylococcus aureus (24 mm), Escherichia coli (25 mm), and Klebsiella pneumoniae (27 mm), outperforming hyaluronic acid alone and showing activity comparable to standard antibiotics, with a minimum inhibitory concentration (MIC) of 15.62 µg/mL. Notably, Se/HA NPs showed pronounced antifungal activity against Candida albicans, with an inhibition zone of 34 mm and an MIC of 7.8 µg/mL. In MG-63 osteosarcoma cells, Se/HA NPs demonstrated potent cytotoxicity, with a half-maximal inhibitory concentration (IC50) of 8.36 µg/mL compared with 746.37 µg/mL for hyaluronic acid. Moreover, Se/HA NPs enhanced wound closure to 73.41% and showed strong anti-inflammatory activity, with an IC50 of 5.37 µg/mL, demonstrating multifunctional bioactivity.