Therapeutic Ultrasound Contrast Agents for the Enhancement of Tumor Diagnosis and Tumor Therapy

Abstract

The functionality of ultrasound in early cancer detection is limited because of its relatively low contrast resolution. Because it has a high degree of echogenicity, a microbubble contrast agent is often used to overcome this intrinsic limitation of imaging at low-contrast resolution. A targeted and drug-loaded microbubble contrast agent for simultaneous diagnosis and therapy has recently been investigated. However, no optimized theragnosis ultrasound microbubbles have been developed. Paclitaxel (PTX)-encapsulating human serum albumin nanoparticles (PTX-HSA-NPs) were conjugated onto an ultrasound microbubbles (PTX-HSA-NPs-MBs) fabricated in the laboratory to result in a narrow size distribution (1.7 +/- 0.7 mu m) and an optimal resonance frequency of 3 MHz. After intravenous injection of HSA-NPs-MBs, echogenicity in the tumor xenografted with breast cancer MCF-7 cells was significantly enhanced, showing the possibility of early cancer diagnosis. Mice injected with PTX-HSA-NPs-MBs showed higher survival rates in comparison with control groups, demonstrating the possibility of theragnosis. In the present study, the conjugation of PTX-HSA-NPs onto the ultrasound microbubbles simultaneously provided (1) enhanced ultrasound signal generation, (2) sufficient drug-loading capacity, (3) ability to deliver drugs to a preferred tumor site, and (4) increased stability in blood circulation.