Antibacterial activity and mechanistic insights of gallium-based nanoparticles: an emerging frontier in metal-based antimicrobials

Abstract

The global rise of antimicrobial resistance has intensified the search for novel therapeutic agents that act through non-conventional mechanisms. Gallium-based nanoparticles (GaNPs) represent a promising yet underexplored class of metal-based antimicrobials. Owing to their unique ability to mimic iron(iii), GaNPs disrupt key bacterial metabolic processes, particularly those dependent on iron acquisition and utilization. This mini-review provides an overview of recent advances in the development and application of GaNPs for antibacterial therapy. Emphasis is placed on their mechanisms of action, spectrum of activity, and potential biomedical applications. The review also discusses emerging insights into bacterial responses to gallium, including resistance dynamics and synergy with existing antibiotics. As an innovative approach to combat multidrug-resistant pathogens, GaNPs offer a compelling alternative to traditional antimicrobials.

Fig. 1. Bacterial iron/heme uptake pathways. Feo system: bacterial ferrous iron transport. HitABC: a ferric iron ABC transport system. Ferritin: there are two types of bacterial iron storage proteins, bacterial ferritin and bacterioferritin.

Fig. 2. Schematic diagram of the uptake of gallium-based compounds through iron/heme acquisition pathways and their proposed intracellular targets.

Fig. 3. The enhanced anti-bacterial activity of four dimethyl gallium 8-quinolinol complexes was determined in physiological relevant low-iron media. Exceptional activity was observed toward a multi-drug resistance strain of the ESKAPE pathogen K. pneumoniae. Protein-uptake studies suggest the methyl substituted complexes do not undergo rapid uptake or exchange with iron-binding proteins.

Fig. 4. The inhibitory effect of gallium-based nanoparticles (GaNPs) on biofilm formation in Pseudomonas aeruginosa and Staphylococcus aureus. GaNPs disrupt bacterial quorum sensing and iron acquisition pathways, impairing biofilm maturation and enhancing susceptibility to treatment.

Fig. 5. In vitro bactericidal effect and inhibiting biofilm formation of ICG-Ga NPs against ESBL E. coli. (A) The SEM images of ESBL E. coli after different treatment and (B) the respective mapping analysis. (C) TEM images of the treated ESBL E. coli. (D) 3D confocal laser scanning microscopy images (size: 630 μm × 630 μm) of ESBL E. coli biofilms after different treatments. Biofilms were stained by SYTO9. The live bacteria can be observed with green fluorescence.

Fig. 6. Synergistic antibacterial mechanisms of gallium-based nanoparticles (GaNPs) and antibiotics.

Fig. 7. In vitro antibacterial viability of ICG-Ga NPs against ESBL E. coli. (A) Survival rates of ESBL E. coli after incubation with ICG-Ga NPs at different concentrations (0, 3.125, 6.25, 12.5, and 25 μg mL⁻¹) at 37 °C in LB medium for 24 h. (B) Survival rates of ESBL E. coli under an 808 nm laser irradiation at the different power intensity (0, 0.1, 0.25, 0.5, 0.75, and 1 W cm⁻²) after incubation with ICG-Ga NPs of 25 μg mL⁻¹ at 37 °C in LB medium for 24 h. (C) Survival rates of ESBL E. coli irradiated by an 808 nm laser irradiation at the power density of 1.0 W cm⁻² for 10 min after incubation with 25 μg mL⁻¹ ICG-Ga NPs or ICG. (D) Optic photographs of bacterial colonies formed by the treated ESBL E. coli in all groups and (E) the corresponding CFU counts. (F) Fluorescent images of ESBL E. coli, stained by DCFH-DA, upon an 808 nm laser irradiation (1 W cm⁻², 10 min) after incubation with 25 μg mL⁻¹ ICG-Ga NPs or ICG. (G) Flow cytometry analysis of ESBL E. coli quantifies the generation of ROS by staining with DCFH-DA. (H) The fluorescence images of the treated ESBL E. coli, stained by SYTO9 and propidium iodide (PI) dyes. (*p < 0.05) Comparison of In vitro antibacterial ability on ESBL E. coli and E. coli between (I) ICG-Ga NPs and (J) Penicillin..

Fig. 8. In vitro bactericidal effect and inhibiting biofilm formation of ICG-Ga NPs against ESBL E. coli. (A) The SEM images of ESBL E. coli after different treatment and (B) the respective mapping analysis. (C) TEM images of the treated ESBL E. coli. (D) 3D confocal laser scanning microscopy images (size: 630 μm × 630 μm) of ESBL E. coli biofilms after different treatments. Biofilms were stained by SYTO9. The live bacteria can be observed with green fluorescence.

Fig. 9. Microstructure of Ga³⁺ -treated E. coli cells. (a) An overview. (b) A large gap between the cell membrane and cell wall (black arrow) and intracellular high-density electronic granules (white arrow). (c) Strip-type electron-dense substances inside the electron-light region (black arrow), and intracellular high electron density granules (white arrow). (d) High electron density granules adhere to the cell wall. (e) and (f) Cells composed of a large electron-light region with substances sporadically distributed.

Fig. 10. Representative photographs taken at the beginning, 3rd day and 7th day of the P. aeruginosa infected wound after being treated with distilled water (negative control), Ga–LTf (experimental group) and tobramycin (positive control)