Green synthesis of hyaluronic acid coated cadmium sulfide nanoparticles with enhanced antibacterial activity

The escalating threat of multidrug-resistant (MDR) pathogenic bacterial strains underscores the urgent need for the development of novel antimicrobial agents. Herein, we report the first-time green synthesis of cadmium sulfide nanoparticles (CdSNPs) using Citrullus colocynthis followed by surface coating with hyaluronic acid (HA) to improve their stability, enhance their antibacterial activity, and reduce cadmium toxicity. The nanoparticles were synthesized using C. colocynthis seed extract in combination with CdSO4·8H2O and Na2S, followed by surface modification with HA. The successful synthesis and coating were confirmed and physically characterized using XRD, FTIR, SEM, and TEM. Antibacterial activity was evaluated through the well diffusion method, minimum inhibitory concentrations (MICs), and anti-biofilm assay using the microtiter plate assay. The results indicated successful synthesis of crystalline, spherical nanoparticles with average sizes of 55.8 nm and 54.7 nm for CdSNPs and CdSNPs-HA, respectively. Antibacterial activity assays indicated that CdSNPs-HA with 0.1 g/mL achieved significantly larger inhibition zones against Staphylococcus aureus (33 mm), followed by Pseudomonas aeruginosa (24 mm), Klebsiella pneumoniae (23 mm), and Escherichia coli (17 mm), outperforming the uncoated CdSNPs (0.1 g/mL) and standard antibiotics tested under the same conditions. The MIC results for CdSNPs-HA were significantly lower than those for CdSNPs, with effective concentration values of 0.09 mg/mL for S. aureus, 0.39 mg/mL for P. aeruginosa, 1.56 mg/mL for E. coli, and 3.12 mg/mL for K. pneumoniae. Notably, CdSNPs-HA at its MIC value of 3.12 mg/mL inhibited the biofilm formation of K. pneumoniae by up to 92%, surpassing the effects of CdSNPs (88%), HA alone (54%), and the seed extract (38%). Furthermore, the sub-MIC of CdSNPs-HA with a concentration of 1.56 mg/mL delayed the growth of K. pneumoniae, prolonged its lag phase, and significantly altered bacterial morphology, as confirmed by TEM analysis. The synthesized CdSNPs-HA demonstrated low hemolytic toxicity, suggesting improved biocompatibility. These results indicate the potential of CdSNP-HA as a promising antimicrobial nanomaterial for managing MDR infections.