Amphiphilic Janus nanoparticles for nitric oxide synergistic photodynamic eradication of MRSA biofilms

Biofilms pose significant threats to public health by causing persistent clinical infections. The development of innovative antibacterial approaches for eliminating biofilms is an urgent necessity. In this study, we developed amphiphilic Janus nanoparticles (JNPs), loaded with hydrophobic chlorin e6 (Ce6) and hydrophilic S-nitrosoglutathione (GSNO), denoted as Ce6-PDA/CaP-GSNO, with the aim to effectively eradicate biofilms and combat methicillin-resistant Staphylococcus aureus (MRSA) infections through nitric oxide (NO) synergistic photodynamic therapy (PDT). Ce6-PDA/CaP-GSNO demonstrated remarkable biofilm penetration ability, efficiently reaching the acidic inner layers, which triggered the rapid release of GSNO, resulting in the generation of an abundant supply of NO. NO not only exhibited potent bactericidal activity but also effectively lowered the GSH level of the biofilm, leading to enhanced efficacy of Ce6. Additionally, the interaction between NO and reactive oxygen species (ROS) resulted in the generation of reactive nitrogen species (RNS), further enhancing PDT efficacy both in vitro and in vivo. In summary, Ce6-PDA/CaP-GSNO demonstrated remarkable biofilm penetration capacity and effective reduction of the GSH level in the biofilms, leading to enhanced PDT efficacy at low photosensitizer doses and laser intensities, thereby minimizing adverse effects on normal tissues. These findings highlight the promising potential of our approach for combating biofilm-related infections. In this study, Janus nanoparticles, Ce6-PDA/CaP-GSNO, were constructed to effectively eradicate biofilms and combat methicillin-resistant Staphylococcus aureus (MRSA) infections through nitric oxide (NO) synergistic photodynamic therapy.