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 hemin in conjunction with the traditional antibiotic of ampicillin was successfully encapsulated into a three-dimensional macromolecular framework of bovine serum albumin (BSA) 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 Staphylococcus aureus (MRSA). 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.