Enhanced Sonodynamic Bacterial Elimination and Wound Healing Therapy Based on Lanthanide Ion Doped Bi2WO6 Nanosheets and Hydrogel Platform

Abstract

Sonodynamic therapy (SDT) offers tremendous potential in preventing multidrug-resistant bacterial infections, as it is noninvasive and requires no antibiotic dependence, effectively addressing the issue of bacterial resistance. This study implements an ultrasound (US) responsive 2D Bi₂WO₆ nanosheets (BWO NSs) as sonosensitizers to generate reactive oxygen species (ROS), resulting in sonodynamic broad-spectrum bacterial elimination. Notably, lanthanide Ytterbium ions are introduced (BWO-x%Yb NSs) to boost the generation of ROS, leading to an enhanced antibacterial effect. The RNA sequencing further reveals the underlying antibacterial mechanism, wherein ROS induces lipid oxidation in bacterial cell membranes and deterioration of membrane integrity, ultimately leading to cellular death. In vitro experiments verify that BWO-x%Yb NSs sonosensitizers attain 100% elimination on Methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli) under US irradiation, demonstrating a broad-spectrum bactericidal ability. Furthermore, to improve the biocompatibility for in vivo SDT, BWO-x%Yb NSs are integrated with hydrogel, serving as a sonosensitizer-hydrogel platform. This platform expedites the healing process of MRSA-infected wounds under ultrasonic stimulation and reduces the wound area by 75% in 10 Days. Therefore, this work highlights the potential of 2D BWO NSs as US-responsive sonosensitizers and a prospective biocompatible sonosensitizer-hydrogel platform for in vivo SDT applications.