title: Nanobubble-Affibody: Novel ultrasound contrast agents for targeted molecular ultrasound imaging of tumor.
abstract: Nanobubbles (NBs), as novel ultrasound contrast agents (UCAs), have attracted increasing attention in the field of molecular ultrasound imaging for tumors. However, the preparation of uniform-sized NBs is considered to be controversial, and poor tumor selectivity in in vivo imaging has been reported. In this study, we fabricated uniform nano-sized NBs (478.2 ± 29.7 nm with polydispersity index of 0.164 ± 0.044, n = 3) using a thin-film hydration method by controlling the thickness of phospholipid films; we then conjugated the NBs with Affibody molecules to produce nano-sized UCAs referred to as NB-Affibody with specific affinity to human epidermal growth factor receptor type 2 (HER2)-overexpressing tumors. NB-Affibody presented good ultrasound enhancement, demonstrating a peak intensity of 104.5 ± 2.1 dB under ultrasound contrast scanning. Ex vivo experiments further confirmed that the NB-Affibody conjugates were capable of targeting HER2-expressing tumor cells in vivo with high affinity. The newly prepared nano-sized NB-Affibody conjugates were observed to be novel targeted UCAs for efficient and safe specific molecular imaging and may have potential applications in early cancer quantitative diagnosis and targeted therapy in the future.
authors.affiliation: Department of Ultrasound Diagnosis, Tang Du Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Hengli
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Ultrasound Diagnosis, Tang Du Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Cai
authors.affiliation: Department of Ultrasound Diagnosis, Tang Du Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Ultrasound Diagnosis, Tang Du Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Lv
authors.affiliation: Department of Pharmaceutical Analysis, Fourth Military Medical University, Xi'an, China.
authors.forename: Youbei
authors.initials: Y
authors.lastname: Qiao
authors.affiliation: Institute of Ultrasound Imaging, Department of Ultrasound, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical Analysis, Fourth Military Medical University, Xi'an, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Ultrasound Diagnosis, Tang Du Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Yilin
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Ultrasound Diagnosis, Tang Du Hospital, Fourth Military Medical University, Xi'an, China. Electronic address: lizhyhl@hotmail.com.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Ultrasound Diagnosis, Tang Du Hospital, Fourth Military Medical University, Xi'an, China. Electronic address: duanyy@fmmu.edu.cn.
authors.forename: Yunyou
authors.initials: Y
authors.lastname: Duan
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media; D003952:Diagnostic Imaging / Q000379:methods*; D005260:Female; D005629:Frozen Sections; D006801:Humans; D008081:Liposomes / Q000648:ultrastructure; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000000981:diagnostic imaging*; D011993:Recombinant Fusion Proteins; D014465:Ultrasonics; D014463:Ultrasonography
chemical_list: D003287:Contrast Media; D008081:Liposomes; D011993:Recombinant Fusion Proteins
keywords: Affibody; HER2; Molecular imaging; Nanobubbles; Ultrasound contrast agents