Gallium-EGCG nanoparticles: a highly biocompatible multifunctional platform with iron-dependent 'Trojan horse'...

The global crisis of multidrug-resistant bacterial infections, coupled with the cytotoxicity of conventional metal-based therapeutics, necessitates the development of highly biocompatible antimicrobial agents. In this work, we have developed gallium (Ga)-based nanoparticles integrated with EGCG (Ga-EGCG NPs), which demonstrated potent antibacterial activity with excellent biocompatibility in both in ovo (chick chorioallantoic membrane) and in vitro (MTT and hemolysis) assays. Comprehensive characterisation using UV-vis, FT-IR, TEM and XPS confirmed the successful synthesis of spherical Ga-EGCG NPs. Consistent with gallium's 'Trojan horse' mechanism exploiting bacterial iron-uptake pathways, antibacterial efficacy depended strongly on iron availability. Under iron-limited conditions, Ga-EGCG NPs demonstrated significant potency, with MIC values of 5 µg mL^-1 against Bacillus subtilis, 50 µg mL^-1 against Escherichia coli 739, 100 µg mL^-1 against Escherichia coli 443, 100 µg mL^-1 against Pseudomonas aeruginosa and 250 µg mL^-1 against methicillin-resistant Staphylococcus aureus (MRSA). Conversely, significantly higher MICs in iron-rich media highlighted the critical role of iron competition. Beyond growth inhibition, Ga-EGCG NPs effectively inhibited biofilms and induced reactive oxygen species (ROS) generation, as confirmed by DCFH-DA assays. SEM imaging and live/dead staining further revealed compromised bacterial cell membranes upon treatment with NPs. Additionally, Ga-EGCG NPs displayed strong antioxidant activity in DPPH and ABTS assays. Importantly, Ga-EGCG NPs exhibited no observable toxicity in the in ovo model, minimal hemolysis (<10%) even at 250-fold MIC, and negligible cytotoxicity toward L6 and 3T3-L1 cell lines, highlighting their superior biocompatibility. Overall, these findings establish Ga-EGCG NPs as a highly biocompatible, iron-dependent antibacterial agent and as a safer alternative to existing antimicrobial strategies.