ROS-responsive conjugated polymer nanoparticles triggered by ultrasound for camptothecin release in breast cancer combination therapy

The treatment of breast cancer (BC) remains a major challenge. Although chemotherapy is currently the most common treatment, it is limited by high side effects. Responsive drug delivery systems (DDS) enable the controlled release of drugs, which can decrease the side effects of chemotherapy and improve efficacy. However, achieving precise delivery and targeted release of drugs is a major challenge. Here, we present ultrasound-triggered reactive oxygen species (ROS)-responsive conjugated polymer nanoparticles for combination therapy of BC. The conjugated polymer nanoparticles are candidates for the development of potential acoustic sensitizers due to their structural properties with good stability and biocompatible acoustic activation properties. In this study, sono-sensitive polymer nanoparticles (SPN) were used for spatiotemporally controlled sonodynamic therapy (SDT) and ROS-responsive chemotherapy. It was demonstrated that the SPN possessed potent acoustic-dynamic properties and could be activated by ultrasound to generate high levels of ROS, which cleaved ROS-responsive junctions, thereby facilitating the release of camptothecin. Furthermore, the SPN exhibited good long circulation properties and biocompatibility <i>in vivo</i>. The SPN combined with ultrasound treatment showed significant therapeutic effects in both BC cell lines and hormonal mouse models, with tumor suppression rates as high as 76.98 ± 9.09%, and no cardiotoxicity or other side effects were observed. Therefore, the present study provides a feasible strategy for designing novel controlled-release drug systems to improve the therapeutic efficacy of BC.