Engineering nanosensitizers into hierarchical modulators for sonodynamic antibacterial therapy

Abstract

The global escalation of antimicrobial resistance necessitates new therapeutic solutions beyond conventional antibiotics. Sonodynamic therapy (SDT) has emerged as a promising non-pharmacological approach that utilizes ultrasound to activate sonosensitizers for localized reactive oxygen species (ROS) generation with high spatiotemporal controllability, offering great potential for treating deep-seated bacterial infections. Compared with organic sonosensitizers which often suffer from poor aqueous solubility and limited target specificity, heterojunction-based nano-sonosensitizers provide a versatile nanoplatform for enhanced SDT by enabling efficient ROS generation and intrinsic multifunctional integration. Current reviews primarily focus on general categories of nano-sonosensitizers or multifunctional SDT platforms in combination with other therapies in the antibacterial field, with insufficient attention to heterojunction engineering. Furthermore, existing discussions on heterostructure design rarely establish clear links to function-dominated antibacterial performance. To address these gaps, this review introduces a systematic, function-oriented hierarchical engineering framework for designing next-generation heterojunction-based SDT nanoplatforms across three synergistic levels: (1) engineering material architecture via conventional, piezoelectric, and catalytically augmented heterojunctions to maximize ROS generation; (2) constructing microenvironment-responsive antibacterial executors that leverage heterostructures to penetrate and eradicate biofilms; and (3) orchestrating programmable antibacterial executors that integrate heterojunction nano-sonosensitizers with multimodal therapies, functioning as an augmentable core, a cooperative partner, or a programmable initiator of therapeutic cascades. Finally, the main translational challenges and future perspectives are discussed.