NIR-II conjugated polymers for tumor sonodynamic therapy

Abstract

Sonodynamic therapy (SDT) utilizes ultrasound to activate sonosensitive agents, generating reactive oxygen species (ROS) within tumor cells to induce oxidative damage. The advantages of ultrasound, such as deep tissue penetration, non-invasiveness, and spatial controllability, make it a promising candidate for cancer treatment. However, its practical application is still limited by factors such as low in vivo delivery efficiency, tumor hypoxia and antioxidant defense mechanisms, insufficient conversion of immunogenic cell death into durable anti-tumor immunity, and the lack of standardized ultrasound parameters, ROS quantification, and material quality control. Near-infrared II (NIR-II) conjugated polymers offer a promising platform because their tunable π-conjugated backbone, stable nano-assembly structure, organic composition, and modular design allow for the integration of imaging, ultrasound-triggered ROS generation, drug delivery, and immune microenvironment modulation into a single system. This article reviews recent research progress in NIR-II conjugated polymer SDT for cancer treatment. First, the physicochemical mechanisms, ROS generation pathways, and validation methods of sonodynamic therapy (SDT) are discussed, and conjugated polymers are compared with traditional small molecule and inorganic/semiconductor sonosensitive agents. This paper analyzes the significance of near-infrared II (NIR-II) imaging for surgical drug delivery (SDT) in terms of drug tracing, tumor localization, and therapeutic window. It further discusses the molecular design, aggregation state regulation, degradability, nanoassembly, delivery, and translational applications of organic conjugated polymer materials. Tumor-related barriers, including hypoxia, delivery obstacles, immunosuppressive microenvironment, and metabolic disorders, are then analyzed, and representative combined therapy strategies involving oxygen supply, chemotherapy, immunotherapy, myeloid cell remodeling, and matrix modulation are summarized. Finally, the challenges faced by materials in NIR-II signal quantification, ROS validation, long-term biosafety, ultrasound dosimetry, and clinical translation are discussed.