Pulsed liquid-based nanoparticle synthesis has emerged as a versatile and environmentally friendly approach for producing a wide range of nanomaterials with tunable properties. Unlike conventional chemical methods, pulsed techniques—such as pulsed laser ablation in liquids (PLAL), electrical discharge, and other energy-pulsing methods—enable the synthesis of high-purity nanoparticles without the need for toxic precursors or stabilizing agents. This review provides a comprehensive overview of the fundamental mechanisms driving nanoparticle formation under pulsed conditions, including plasma–liquid interactions, cavitation, and shockwave dynamics. We discuss the influence of key synthesis parameters, explore different pulsed energy sources, and highlight the resulting effects on nanoparticle size, shape, and composition. The review also surveys a broad spectrum of material systems and outlines advanced characterization techniques for analyzing synthesized nanostructures. Furthermore, we examine current and emerging applications in biomedicine, catalysis, sensing, energy, and environmental remediation. Finally, we address critical challenges such as scalability, reproducibility, and mechanistic complexity, and propose future directions for advancing the field through hybrid synthesis strategies, real-time diagnostics, and machine learning integration. By bridging mechanistic insights with practical applications, this review aims to guide researchers toward more controlled, sustainable, and innovative nanoparticle synthesis approaches.

Gold nanoparticles (AuNPs) synthesized via picosecond pulsed laser ablation were investigated as enhancers of methylene blue (MB)-mediated photodynamic therapy (PDT) against Escherichia coli. AuNPs produced at 532 and 1064 nm with frequencies of 20–50 kHz showed frequency- and size-dependent effects, with 50 kHz yielding the highest particle concentrations and smaller particles enhancing reactive oxygen species (ROS) generation. UV-Vis and fluorescence spectroscopy confirmed nanoparticle formation and plasmonic properties consistent with TEM measurements. Photobleaching assays demonstrated that AuNPs significantly increased MB singlet oxygen generation, while the efflux pump inhibitor INF-55 further amplified bacterial killing without altering net ROS yield. In vitro assays revealed that INF-55 combined with MB/AuNPs achieved ~59% higher bacterial deactivation compared to MB/AuNPs alone. Molecular docking confirmed stronger binding of INF-55 to the AcrB efflux pump (−9.1 kcal/mol) than MB, supporting its role as a competitive inhibitor that promotes intracellular MB retention. These findings establish a dual-action PDT strategy in which AuNPs enhance ROS production and INF-55 augments antibacterial efficacy via efflux pump inhibition. Together, this platform provides a proof of concept for future translation to biofilm- and tissue-based infection models, and potentially to localized clinical applications such as prosthetic joint, catheter-associated, or chronic wound infections where conventional sterilization or systemic antibiotics are insufficient.