Bioactive Nanotherapeutic Ultrasound Contrast Agent for Concurrent Breast Cancer Ultrasound Imaging and Treatment.

Abstract

Contrast-enhanced ultrasound (CEUS) plays a crucial role in cancer diagnosis. The use of ultrasound contrast agents (UCAs) is inevitable in CEUS. However, current applications of UCAs primarily focus on enhancing imaging quality of ultrasound contrast rather than serving as integrated platforms for both diagnosis and treatment in clinical settings. In this study, a novel UCA, termed NPs-DPPA(C₃F₈), is innovatively prepared using a combination of nanoprecipitation and ultrasound vibration methods. The DPPA lipid possesses inherent antiangiogenic and antitumor activities, and when combined with C₃F₈, it functions as a theranostic agent. Notably, the preparation of NPs-DPPA(C₃F₈) is straightforward, requiring only one hour from raw materials to the final product due to the use of a single material, DPPA. NPs-DPPA(C₃F₈) exhibits inherent antiangiogenic and biotherapeutic activities, effectively inhibiting triple-negative breast cancer (TNBC) angiogenesis and reducing VEGFA expression both in vitro and in vivo. Clinically, NPs-DPPA(C₃F₈) enables simultaneous real-time imaging, tumor assessment, and antitumor activity. Additionally, through ultrasound cavitation, NPs-DPPA(C₃F₈) can overcome the dense vascular walls to increase accumulation at the tumor site and facilitate internalization by tumor cells. The successful preparation of NPs-DPPA(C₃F₈) offers a novel approach for integrating clinical diagnosis and treatment of TNBC.