Desolvation Synthesis of Peroxidase-like Bovine Serum Albumin-Based Nanoparticles as a Potent Antibiotic Adjuvant To Tackle Drug-Resistant Bacteria.

The devastating occurrence of antibiotic resistance arising from the surrounding environment, such as in healthcare facilities, has posed global threats to public health, urging a continuous search for safe and effective antibacterial agents. Here, the adjuvant activity center of <b>h</b>emin in conjunction with the traditional antibiotic of <b>a</b>mpicillin was successfully encapsulated into a three-dimensional macromolecular framework of bovine serum albumin (<b>B</b>SA) to form hemin-BSA-ampicillin nanoparticles (HBA NPs) via a straightforward desolvation process. Based on the robust peroxidase-like activity of the obtained HBA NPs, a significant quantity of hydroxyl radicals (^•OH) was generated via the Fenton-like reaction. As an electrophilic species, ^•OH may not only facilitate the oxidation of organic substances, leading to observable color reaction, but also effectively inactivate pathogens, including drug-resistant bacteria and viruses, through structural decomposition. Compared to the sole antibacterial effect of ampicillin, HBA NPs exhibited markedly superior antibacterial activity against methicillin-resistant <i>Staphylococcus aureus</i> (<i>MRSA</i>). Furthermore, the formed protein coating on the nanoparticles contributed significantly to the desirable biocompatibility of the obtained nanocomposite. Therefore, the easily prepared, highly biocompatible, and antimicrobial HBA NPs provided a prototype of protein-based antibiotic adjuvants using peroxidase-like nanomaterials with promising therapeutic potential to tackle emerging drug-resistant infectious microbes.