Gallium-Loaded Polydopamine Nanoparticles as a Selective Photothermal Antibiofilm System

Bacterial biofilm infections are a major cause of hospital-acquired infections globally. Metal-loaded photothermal polymers show effective antibiofilm properties by combining ions with heat. However, the main obstacles to these polymers include lack of selectivity, side effects induced by high local photothermal temperatures, and the potential toxicity of released ions. The pH-responsive chelation between polydopamine (PDA) and metal ions may result in selective ion release near the biofilm, reducing ion toxicity while exhibiting synergistic antibiofilm properties at low photothermal temperatures. Herein, biosafe gallium-loaded PDA (Ga³⁺/PDA) nanoparticles were prepared in an acidic Ga³⁺/hydrogen peroxide system for the first time. Dopamine polymerization under acidic conditions prevented Ga³⁺ hydrolysis. Ga³⁺/PDA had a narrower pH range (7.4–5.5) for charge reversal and ion release than copper-loaded PDA (Cu²⁺/PDA) (7.4–3.5). Ga³⁺/PDA demonstrated a pH-responsive inhibition of bacterial growth and biofilm formation. The highest antibacterial and antibiofilm effect was observed at pH 5.5, which is the pH near infection sites. Ga³⁺/PDA and Cu²⁺/PDA exhibited better photothermal antibacterial and antibiofilm effects than PDA, but only Ga³⁺/PDA showed a synergistic antibiofilm effect. The photothermal temperatures of Ga³⁺/PDA for effective antibacterial and antibiofilm capability were ∼45 and ∼50 °C, respectively. Ga³⁺/PDA with or without photothermy effectively inhibited mono- and dual-species biofilms by causing Fe³⁺ deficiency and reducing the expression of genes related to Fe³⁺ metabolism. Ga³⁺/PDA exhibited no significant toxicity toward blood cells or human embryonic hepatocyte cells. Overall, Ga³⁺/PDA is a reliable and biosafe antibiofilm system with potential clinical applications.