ABSTRACT: Purpose: The growing prevalence of multidrug-resistant (MDR) bacteria makes it clinically urgent to develop an agent able to detect and treat infections simultaneously. Silver has served as a broad-spectrum antimicrobial since ancient times but suffers from major challenges such as moderate antimicrobial activity, nonspecific toxicity, and difficulty to be visualized in situ. Here, we propose a new photoactive silver nanoagent that relies on a photosensitizer-triggered cascade reaction to liberate Ag+ on bacterial surfaces exclusively, allowing the precise killing of MDR bacteria. Additionally, the AgNP core acts as a backgroundless surface-enhanced Raman scattering (SERS) substrate for imaging the distribution of the nanoagents on bacterial surfaces and monitoring their metabolic dynamics in the infection sites. Methods: In this strategy, the photoactive antibacterial AgNP was decorated with photosensitizers (Chlorin e6, Ce6) and Raman reporter (4-Mercaptobenzonitrile, 4-MB) to provide new opportunities for clinically monitoring and fighting MDR bacterial infections. Upon 655 nm laser activation, the Ce6 molecules produce ROS efficiently, triggering the rapid release of Ag+ from the AgNP core to kill bacteria. Poly[4-O-(α-D-glucopyranosyl)-D-glucopyranose] (GP) was introduced as bacteria-specific targeting ligands. SERS spectra of the prepared GP-Ce6/MB-AgNPs were recorded after injecting for 0.5, 4, 8, 12, 24, and 48 h to track the dynamic metabolism of the nanoagents and thus guiding the antibacterial therapy. Results: This new antimicrobial strategy exerts a dramatically enhanced antibacterial activity. The in vitro antibacterial efficiencies of this non-antibiotic technique were up to 99.6% against Methicillin-resistant Staphylococcus aureus (MRSA) and 98.8% against Escherichia coli (EC), while the in vivo antibacterial efficiencies for MRSA- and Carbapenem-resistant Pseudomonas aeruginosa (CRPA)-infected mice models were 96.8% and 93.6%, respectively. Besides, backgroundless SERS signal intensity of the wound declined to the level of normal tissue until 24 h, indicating that the nanoagents had been completely metabolized from the infected area. Conclusion: Given the backgroundless monitoring ability, high antibacterial efficacy, and low toxicity, the photoactive cascading agents would hold great potential for MDR-bacterial detection and elimination in diverse clinical settings.
