Lighting Up the Gold Nanoclusters via Host–Guest Recognition for High-Efficiency Antibacterial Performance and Imaging

Au nanoclusters (Au NCs) with a unique size effect on the antibacterial performance provide a promising nanoprobe for developing an efficient nanomedicine. However, little progress has been made owing to the low quantum yield and poor stability of Au NCs. In this work, protamine (Prot) functionalized Au NCs (Prot/MTU-Au NCs) with high stability were achieved through a simple mixing with 6-methyl-2-thiouracil-capped Au NCs (MTU-Au NCs) due to the hydrogen bonding between 5-methyl-2-thiouracil (MTU) and the guanidine groups from Prot. Interestingly, a distinctly enhanced photoluminescence from Prot/MTU-Au NCs (ca. 28-fold) was observed due to the formation of rigid host–guest assemblies. We inferred that the cross-linked structure and supramolecular hydrogen bonds both contributed to the fluorescence enhancement and stability. The extra small size of the NCs and the efficient antibacterial capability from the capping shell of Prot encouraged us to probe its antibacterial performance systemically. It was found that the Prot/MTU-Au NCs with highly stable loading of positively charged antibacterial reagents were likely to penetrate into the bacteria and thus enhance the ability to kill both Gram-negative bacteria (Escherichia coli) and Gram-positive bacteria (multiple-resistant Staphylococcus aureus). The synergetic effect between the unique size and the capping layers enabled the minimal inhibitory concentration of the as-derived Prot/MTU-Au NCs reduced by ∼100-fold compared to that with individual Au nanoparticle. The antibacterial mechanism further revealed that membrane injury occurred and reactive oxygen species were generated after the incubation of the bacteria with Prot/MTU-Au NCs. Moreover, the highly luminescent fluorescence and positive surface charge of Prot/MTU-Au NCs could image the bacteria easily, which held great potential for imaging-guided antibacterial platform.