Nanosized Phase-Changeable "Sonocyte" for Promoting Ultrasound Assessment

Despite the ability of microbubble contrast agents to improve ultrasound diagnostic performance, their application potential is limited due to low stability, fast clearance, and poor tissue permeation. This study presents a promising nanosized phase-changeable erythrocyte (Sonocyte), composed of liposomal dodecafluoropentane coated with multilayered red blood cell membranes (RBCm), for improving ultrasound assessments. Sonocyte is the first RBCm-functionalized ultrasound contrast agent with uniform nanosized morphology, and exhibits good stability, systemic circulation, target-tissue accumulation, and even ultrasound-responsive phase transition, thereby satisfying the inherent requirement of ultrasound imaging. It is identified that Sonocyte displays similar sensitivity as microbubble SonoVue, a clinical ultrasound contrast agent, for effectively detecting normal parenchyma and hepatic necrosis. Importantly, compared with SonoVue lacking of ability to detect tumors, Sonocyte can identify tumors with high sensitivity and specificity due to superior tumor accumulation and penetration. Therefore, Sonocyte exhibits superior capabilities over SonoVue, endowing with a great clinical application potential.