De Novo Designed Ru(II) Metallacycle as a Microenvironment-Adaptive Sonosensitizer and Sonocatalyst for Multidrug-Resistant Biofilms Eradication.

Albeit sonodynamic therapy (SDT) has achieved encouraging progress in microbial sterilization, the scarcity of guidelines for designing highly effective sonosensitizers and the intricate biofilm microenvironment (BME), substantially hamper the therapeutic efficacy against biofilm infections. To address the bottlenecks, we innovatively design a Ru(II) metallacycle-based sonosensitizer/sonocatalyst (named Ru-A3-TTD) to enhance the potency of sonotherapy by employing molecular engineering strategies tailored to BME. Our approach involves augmenting Ru-A3-TTD's production of ultrasonic-triggered reactive oxygen species (ROS), surpassing the performance of commercial sonosensitizers, through a straightforward but potent π-expansion approach. Within the BME, Ru-A3-TTD synergistically amplifies sonotherapeutic efficacy via triple-modulated approaches: (i) effective alleviation of hypoxia, leading to increased ROS generation, (ii) disruption of the antioxidant defense system, which shields ROS from glutathione consumption, and (iii) enhanced biofilm penetration, enabling ROS production in deep sites. Notably, Ru-A3-TTD sono-catalytically oxidizes NADPH, a critical coenzyme involved in antioxidant defenses. Consequently, Ru-A3-TTD demonstrates superior biofilm eradication potency against multidrug-resistant Escherichia coli compared to conventional clinical antibiotics, both in vitro and in vivo. To our knowledge, this study represents the pioneering instance of a supramolecular sonosensitizer/sonocatalyst. It provides valuable insights into the structure-activity relationship of sonosensitizers and paves a promising pathway for the treatment of biofilm infections.

A novel surface-enhanced Raman based molecular identification platform for multiplexed and highly accurate clinical diagnosis of viral diseases.

During the infection process, the interactions among respiratory viruses impact the dynamics of transmission and clinical outcomes. Therefore, efficient molecular detection methods provide a basis for rational drug use and effective health management. Surface-enhanced Raman scattering (SERS) is an ultra-sensitive spectroscopic technique capable of generating extremely narrow spectra (∼1-2 cm-1), enabling simultaneous detection of multiple targets. By judiciously designing plasmonic nanostructures as SERS substrates, Raman signals can be amplified by several orders of magnitude (∼105-1015), facilitating the detection of trace biomolecules. In this highlight, we highlight the work about a novel SERS platform for the high-precision multi-virus molecular identification. This may offer a highly sensitive, specific, and accurate method for the detection of multiple viruses.