title: Improving performance of nanoscale ultrasound contrast agents using N,N-diethylacrylamide stabilization.
abstract: The design of nanoscale yet highly echogenic agents for imaging outside of the vasculature and for ultrasound-mediated drug delivery remains a formidable challenge. We have previously reported on formulation of echogenic perfluoropropane gas nanobubbles stabilized by a lipid-pluronic surfactant shell. In the current work we describe the development of a new generation of these nanoparticles which consist of perfluoropropane gas stabilized by a surfactant and lipid membrane and a crosslinked network of N,N-diethylacrylamide. The resulting crosslinked nanobubbles (CL-PEG-NB) were 95.2±25.2nm in diameter and showed significant improvement in stability and retention of echogenic signal over 24h. In vivo analysis via ultrasound and fluorescence mediated tomography showed greater tumor extravasation and accumulation with CL-PEG-NB compared to microbubbles. Together these results demonstrate the capabilities and advantages of a new, more stable, nanometer-scale ultrasound contrast agent that can be utilized in future work for diagnostic scans and molecular imaging.
authors: Department of Radiology, Case Western Reserve University, Cleveland, OH, USA. Electronic address: rhp26@case.edu.
authors: Reshani H
authors: RH
authors: Perera
authors: Department of Radiology, Case Western Reserve University, Cleveland, OH, USA. Electronic address: hanping.wu@case.edu.
authors: Hanping
authors: H
authors: Wu
authors: Department of Radiology, Case Western Reserve University, Cleveland, OH, USA. Electronic address: Pmp48@case.edu.
authors: Pubudu
authors: P
authors: Peiris
authors: Department of Radiology, Case Western Reserve University, Cleveland, OH, USA. Electronic address: Cxh404@case.edu.
authors: Christopher
authors: C
authors: Hernandez
authors: Department of Radiology, Case Western Reserve University, Cleveland, OH, USA. Electronic address: alan.burke@case.edu.
authors: Alan
authors: A
authors: Burke
authors: Department of Radiology, Case Western Reserve University, Cleveland, OH, USA. Electronic address: yxz443@case.edu.
authors: Helen
authors: H
authors: Zhang
authors: Department of Radiology, Case Western Reserve University, Cleveland, OH, USA. Electronic address: Agata.exner@case.edu.
authors: Agata A
authors: AA
authors: Exner
mesh_terms: D000178:Acrylamides / Q000737:chemistry*; D000818:Animals; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging; D003287:Contrast Media / Q000737:chemistry*; D016503:Drug Delivery Systems; D006801:Humans; D051379:Mice; D045423:Microbubbles; D053758:Nanoparticles / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D014463:Ultrasonography; D023041:Xenograft Model Antitumor Assays
chemical_list: D000178:Acrylamides; D003287:Contrast Media; D011108:Polymers; C428028:poly(N,N-diethylacrylamide)
keywords: Cancer; Extravasation; Microbubble; Nanobubble; Ultrasound contrast agent