Engineering Reactive Oxygen Species-Responsive Supramolecular Gels with Inherent Antibacterial Activity for Combating Bacterial Infections.

Bacterial infections, particularly those caused by antibiotic-resistant strains, present a serious threat to global public health, highlighting the critical need to develop novel antibacterial agents capable of overcoming multidrug resistance. Supramolecular gels with intrinsic antibacterial activity represent a promising strategy. In this study, we designed and synthesized reactive oxygen species (ROS)-responsive low molecular weight gelators (LMWGs) using a bottom-up approach based on self-antibacterial synthons and ROS-cleavable thioketal. The structure of the gelators was characterized by 1H NMR spectroscopy and high-resolution mass spectrometry (HRMS). Their gelation behavior was systematically investigated, and the critical gelation concentration (CGC) was determined. The self-assembly mechanism of the LMWGs was elucidated through 1H NMR, Fourier transform infrared (FT-IR) spectroscopy, ultraviolet-visible (UV-Vis) spectroscopy, and fluorescence spectroscopy (FS). The ROS-triggered degradation and drug release profiles were also evaluated. Biocompatibility was assessed via CCK-8 assays using L929 and 293T cell lines. The antibacterial efficacy of the blank and ciprofloxacin hydrochloride (CIP·HCl)-loaded supramolecular gels was evaluated against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) through bacterial adhesion assays and plate colony counting methods. The blank supramolecular gel demonstrated strong antibacterial and bactericidal activity against both strains, with efficacy comparable to that of CIP·HCl. The antibacterial application of the blank supramolecular gel was further supported by results from the inhibition zone assay. Notably, due to its membrane-disruptive mechanism, the blank gel also exhibited significant efficacy against methicillin-resistant Staphylococcus aureus (MRSA). This work establishes that the rational design of LMWGs for targeted membrane disruption constitutes a viable strategy to develop novel platforms of self-antibacterial supramolecular gels against drug-resistant bacteria.