Impact of protein corona and light modulation on the antibacterial activity of light-activated silver nanoparticles

Silver nanoparticles (AgNPs) as antimicrobial agents have gained extensive popularity due to their broad-spectrum action. Recently, AgNPs have been combined with photosensitizers (PS) to develop a synergistic antimicrobial effect. This synergy is associated with the light-activated increase in the release of Ag⁺, which drives the antibacterial mechanism against antibiotic-resistant bacteria (ARB). A factor typically not considered in the performance of AgNPs is the environmental conditions, such as salt and protein content, that significantly impact their bactericidal effect. In this work, we used protoporphyrin IX (PpIX) as a PS to synthesize PpIX-AgNPs. We elucidated the critical role of environmental conditions on the colloidal stability of PpIX-AgNPs in different bacterial culture media. We also determined the impact of the culture media on the light-activated release kinetics of Ag⁺. We found that cell media with lower protein and higher salt content drive the colloidal stability and release kinetics of Ag⁺ from AgNPs. Furthermore, we have shown that the multiple-irradiation approach of this light-controlled platform maximizes the release of Ag⁺ and promotes effective antibacterial action. We successfully tested this multiple-irradiation strategy in methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) demonstrating ∼7-log-unit reduction at 1.5 μg mL^-1 of PpIX-AgNP. A 6-log-unit MRSA inhibition was achieved in the nutrient broth (NB) media under the same irradiation strategy. We envision that this light-activated PpIX-AgNPs system can overcome major issues with the elimination of ARB and reduce side effects.