Antibiotic-resistant infections necessitate strategies independent of biochemical targets. Black phosphorus nanosheets (BPNs) offer biophysical antibacterial mechanisms but suffer from rapid oxidative degradation, reliance on photoactivation, limited biological selectivity, and the absence of benign production methods, hindering clinical translation. Here, we report a green, ethanol-assisted, one-step supramolecular engineering strategy in which tannic acid (TA) simultaneously enhances exfoliation efficiency and stabilizes ultrathin BPNs, yielding TA-BPNs with strong colloidal stability and significantly improved oxidation resistance. Crucially, TA-BPNs exhibit a light-independent antibacterial activity via curvature-selective membrane interactions. TA-BPNs preferentially interact with bacterial membranes bearing negative intrinsic curvature, anchor at the membrane via TA-mediated adhesion, concentrate mechanical stress at nanosheet edges, and induce rapid permeabilization and bacterial death. In contrast, mammalian cell membranes, with near-zero intrinsic curvature, remain largely undisturbed, conferring TA-BPNs’ favorable biocompatibility and selectivity. Molecular dynamics simulations and giant unilamellar vesicle assays corroborate the observed curvature-selective antibacterial action. Moreover, TA-BPNs demonstrated robust efficacy in eradicating ex vivo rabbit dental biofilms comprising multiple species and in curing murine systemic infections caused by norfloxacin-resistant Staphylococcus aureus. Extending this supramolecular design to alternative polyphenols (e.g., epigallocatechin gallate) yielded potent antibacterial analogues, validating the platform as a versatile, generalizable approach for tunable antibacterial activity against antibiotic-resistant infections.
Xu et al. (Tue,) studied this question.