Chemical gas-generating nanoparticles for tumor-targeted ultrasound imaging and ultrasound-triggered drug delivery.

Although there is great versatility of ultrasound (US) technologies in the real clinical field, one main technical challenge is the compromising of high quality of echo properties and size engineering of ultrasound contrast agents (UCAs); a high echo property is offset by reducing particle size. Herein, a new strategy for overcoming the dilemma by devising chemical gas (CO2) generating carbonate copolymer nanoparticles (Gas-NPs), which are clearly distinguished from the conventional gas-encapsulated micro-sized UCAs. More importantly, Gas-NPs could be readily engineered to strengthen the desirable in vivo physicochemical properties for nano-sized drug carriers with higher tumor targeting ability, as well as the high quality of echo properties for tumor-targeted US imaging. In tumor-bearing mice, anticancer drug-loaded Gas-NPs showed the desirable theranostic functions for US-triggered drug delivery, even after i.v. injection. In this regard, and as demonstrated in the aforementioned study, our technology could serve a highly effective platform in building theranostic UCAs with great sophistication and therapeutic applicability in tumor-targeted US imaging and US-triggered drug delivery.

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

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 µm) 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.