Nanosized Ultrasound Enhanced-Contrast Agent for in Vivo Tumor Imaging via Intravenous Injection

Abstract

To enhance the detection limit of ultrasound (US) imaging, ultrasound enhanced-contrast agents (UECAs) that can go preferentially to the target tissue such as a tumor and amplify the US signal have been developed. However, nanosized UECAs among various UECAs developed are very limited to clearly demonstrate proper ability for selective tumor detection by US imaging upon their intravenous injection. In this study, we prepared CaCO3 nanoparticles that were formed inside a flexible and biocompatible pluronic-based nanocarrier. This nanosized UECA was stable in serum-containing media and generated CO2, more preferentially at low pH; thus, it could be detected by US imaging. After intravenous injection into tumor-bearing mice, this nanosized UECA showed a significant US contrast enhancement at the tumor site in 1 h, in contrast to no change in the liver, followed by a rapid clearance from the body in 24 h. Therefore, the present nanosized UECA could be applied as an effective diagnostic modality for in vivo tumor imaging by ultrasonography.

Gas‐Generating, pH‐Responsive Calcium Carbonate Hybrid Particles with Biomimetic Coating for Contrast‐Enhanced Ultrasound Imaging

“…CaCO 3 particles are an extensively studied pH‐responsive material, not only for their applicability for targeted delivery of active substances but also for their gas‐generating capacity, which provides potential as an ultrasound contrast agent for the detection and imaging of tumor cells 7b,21. These cells have slightly lower extracellular pH levels when compared to normal cells and this can trigger CO 2 production from local CaCO 3 .…”

Core-shell NaGdF4@CaCO3 nanoparticles for enhanced magnetic resonance/ultrasonic dual-modal imaging via tumor acidic micro-enviroment triggering

“…Then, PBS buffer with various pH values from 5.0 to 7.4 was dropped on the samples, and the CO 2 bubble image from NaGdF 4 @CaCO 3 -PEG was obtained by an optical microscope at room temperature 10, 11 .…”

“…Therefore, early diagnosis of cancer is crucial for timely therapy to prevent the potential risk of cancer metastasis and improve the long-term survival. Many non-invasive biomedical imaging techniques have been applied in the diagnosis of cancer including magnetic resonance imaging (MRI) 4–9 , ultrasound imaging (US) 10, 11 , positron emission tomography (PET) 12–15 , and computed X-ray tomography (CT) 16–19 , etc. Among the clinically applied diagnostic modalities, MRI has a high potential to image the tissue pathological changes, as it could safely provide high spatial resolution information 20 .…”

Advanced Microbubbles as a Multifunctional Platform Combining Imaging and Therapy

“…Kim et al prepared CaCO 3 nanoparticles as ultrasound enhanced-contrast agents (UECAs) for tumor ultrasound imaging. In vivo experiment showed this nanosized UECA had a significant US contrast enhancement at the tumor site and was excreted out quickly [42] (Figure 3). Yang fabricated NBs (478.2 ± 29.7 nm in diameter, PDI 0.164 ± 0.044) via a thin-film hydration method, and successfully attached the NBs with biotinylated anti-ErbB2 affibody, which has high affinity and specificity for the HER2 overexpressed in some breast cancer tumors [43].…”