Abstract
BackgroundUltrasound molecular imaging is a novel diagnostic approach for tumors, whose key link is the construction of targeted ultrasound contrast agents. However, available targeted ultrasound contrast agents for molecular imaging of tumors are only achieving imaging in blood pool or one type tumor. No targeted ultrasound contrast agents have realized targeted ultrasound molecular imaging of tumor parenchymal cells in a variety of solid tumors so far. Carbonic anhydrase IX (CAIX) is highly expressed on cell membranes of various malignant solid tumors, so it’s a good target for ultrasound molecular imaging. Here, targeted nanobubbles carrying CAIX polypeptides for targeted binding to a variety of malignant tumors were constructed, and targeted binding ability and ultrasound imaging effect in different types of tumors were evaluated.ResultsThe mean diameter of lipid targeted nanobubbles was (503.7 ± 78.47) nm, and the polypeptides evenly distributed on the surfaces of targeted nanobubbles, which possessed the advantages of homogenous particle size, high stability, and good safety. Targeted nanobubbles could gather around CAIX-positive cells (786-O and Hela cells), while they cannot gather around CAIX-negative cells (BxPC-3 cells) in vitro, and the affinity of targeted nanobubbles to CAIX-positive cells were significantly higher than that to CAIX-negative cells (P < 0.05). Peak intensity and duration time of targeted nanobubbles and blank nanobubbles were different in CAIX-positive transplanted tumor tissues in vivo (P < 0.05). Moreover, targeted nanobubbles in CAIX-positive transplanted tumor tissues produced higher peak intensity and longer duration time than those in CAIX-negative transplanted tumor tissues (P < 0.05). Finally, immunofluorescence not only confirmed targeted nanobubbles could pass through blood vessels to enter in tumor tissue spaces, but also clarified imaging differences of targeted nanobubbles in different types of transplanted tumor tissues.ConclusionsTargeted nanobubbles carrying CAIX polypeptides can specifically enhance ultrasound imaging in CAIX-positive transplanted tumor tissues and could potentially be used in early diagnosis of a variety of solid tumors derived from various organs.
Highlights
Ultrasound molecular imaging is a novel diagnostic approach for tumors, whose key link is the construction of targeted ultrasound contrast agents
When targeted nanobubbles were loaded with Carbonic anhydrase IX (CAIX) polypeptides, the zeta potential increased to −14.80 ± 2.12 mV, implying that the positively charged amino groups on CAIX polypeptides neutralized partial negative charge of anionic phospholipid [27]
The cytotoxicity of targeted and blank nanobubbles on 786-O cells was measured by MTT assay, which showed that the cytotoxicity of targeted nanobubbles and blank nanobubbles at the same concentrations was not significantly different (P > 0.05), indicating that bound polypeptides did not significantly alter the cytotoxicity of nanobubbles (Fig. 1d)
Summary
Ultrasound molecular imaging is a novel diagnostic approach for tumors, whose key link is the construction of targeted ultrasound contrast agents. Available targeted ultrasound contrast agents for molecular imaging of tumors are only achieving imaging in blood pool or one type tumor. Zhu et al J Nanobiotechnol (2017) 15:63 lesions that express specific targets These agents aggregate in target tissues through the blood circulation, achieving targeted ultrasound imaging at the molecular or cellular level [2,3,4]. Because the size of UCAs currently used is 2–8 μm, they only can be used for imaging in blood pool and cannot pass through tumor blood vessels to achieve ultrasound molecular imaging of parenchymal cells in tumor tissues [6]. Due to enhanced permeability and retention (EPR) effect, some studies have shown that nanoscale UCAs with the particle size smaller than 700 nm can be used to achieve targeted ultrasound molecular imaging of tumor parenchyma tissues [7]. Imaging duration time and peak intensity provided by these nanobubbles in transplanted tumors were significantly better than those of blank nanobubbles, which could be used for achieving specific targeted imaging of prostate cancer and providing the research basis and methods for targeted molecular imaging of tumors [11,12,13]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
