Preparation of novel targeting nanobubbles conjugated with small interfering RNA for concurrent molecular imaging and gene therapy in vivo

• Published in: The FASEB journal Vol. 33; no. 12; p. 14129
• Main Authors: Wu, Bolin, Shang, Haitao, Liang, Xitian, Sun, Yixin, Jing, Hui, Han, Xue, Cheng, Wen
• Format: Journal Article
• Language: English
• Published: United States 01.12.2019
• Subjects: low-frequency ultrasound; NET-1; SMMC-7721; hepatocellular carcinoma; Balc/c nude mice
• ISSN: 1530-6860
• DOI: 10.1096/fj.201900716RR

The aim of this study was to establish a novel targeting nanobubble (TNB) conjugated with small interfering RNA (siRNA)-cyanine 5 (Cy5) and to validate its theranostic ability . The TNB conjugated with neuroepithelial transforming gene 1 (NET-1) siRNA-Cy5 was prepared by thin-film hydration and mechanical sonication method. A hepatocellular carcinoma (HCC) xenograft model was established by subcutaneously injecting SMMC-7721 cells in BALB/c nude mice. The NET-1 siRNA-conjugated TNB was utilized for accurate contrast-enhanced ultrasound imaging, which was enabled by the target ligand GPC-3 antibody and specific gene transfection with the aid of low-frequency ultrasound (LFUS) irradiation. BALB/c nude mice bearing tumors were randomized into 5 groups and irradiated with LFUS for 5 min after TNB administration; mice were treated twice a week for a total of 60 d. The mean particle size of TNB was <500 nm. Mice treated with NET-1 siRNA-conjugated TNB showed a significant decrease in tumor growth and the highest survival rate. Our findings offer an effective and safe gene vehicle and probe for molecular imaging . It may improve the early diagnosis and treatment effects of HCC.-Wu, B., Shang, H., Liang, X., Sun, Y., Jing, H., Han, X., Cheng, W. Preparation of novel targeting nanobubbles conjugated with small interfering RNA for concurrent molecular imaging and gene therapy .