Nano-Reactors Based on Ovotransferrin Organic Skeleton through a Ferroptosis-like Strategy Efficiently Enhance Antibacterial Activity

Abstract

The issue of bacterial resistance is an escalating problem due to the misuse of antibiotics worldwide. This study introduces a new antibacterial mechanism, the ferroptosis-like death (FLD) of bacteria, and an approach to creating green antibacterial nano-reactors. This innovative method leverages natural iron-containing ovotransferrin (OVT) assembled into an organic skeleton to encapsulate low-concentration adriamycin (ADM) for synthesizing eco-friendly nano-reactors. FLD utilizes the Fenton reaction of reactive oxygen species and ferrous ions to continuously produce ·OH, which can attack the bacterial cell membrane and destroy the cell structure to achieve bacteriostasis. The OVT@ADM nano-reactors are nearly spherical, with an average diameter of 247.23 nm and uniform particle sizing. Vitro simulations showed that Fe3+ in OVT@ADM was reduced to Fe2+ by glutathione in the bacterial periplasmic space, which made the structure of OVT loose, leading to a sustained slow release of ADM from OVT@ADM. The H2O2 continuously produced by ADM oxidized Fe2+ through the Fenton reaction to produce ·OH and Fe3+. The results of the antibacterial assay showed that OVT@ADM had a satisfactory antibacterial effect against S. aureus, and the inhibition rate was as high as 99.3%. The cytotoxicity results showed that the mitigation strategy significantly reduced the cytotoxicity caused by ADM. Based on the FLD mechanism, OVT@ADM nano-reactors were evaluated and applied to bacteriostasis. Therefore, the novel antibacterial mechanism and OVT@ADM by the green synthesis method have good application prospects.