title: Novel dual-mode nanobubbles as potential targeted contrast agents for female tumors exploration.
abstract: The purpose of this study was to prepare tumor-specific dual-mode nanobubbles as both ultrasound contrast agents (UCAs) and near-infrared fluorescence (NIRF) imaging agents for female tumors. Recent studies have demonstrated the conjugation of anti-tumor ligands on the surface of nanobubbles for use as molecule-targeting ultrasound contrast agents for tumor visualization. However, this complicated procedure has also posed a challenge to nanobubble stability. Thus, in the present study, we combined the fluorescent dye, NIRF IR-780 iodide, which has lipid solubility and tumor-targeting characteristics, with the phospholipid film of nanobubbles that we constructed. We then characterized the physical features of the IR-780-nanobubbles, observed their tumor-targeting capacity in multiple female tumor cell types in vitro, and verified their capability for use in tumor-specific ultrasound contrast imaging and NIRF imaging in vivo. The results showed that the new IR-780-nanobubbles had a uniform nano-size (442.5 ± 48.6 nm) and stability and that they were safe and effective at NIRF imaging and ultrasound imaging in vitro. The IR-780-nanobubbles were found to automatically accumulate on different female tumor cells in vitro with a considerable targeting rate (close to 40 %) but did not accumulate on cardiac muscle cells used as a negative control. Importantly, the IR-780-nanobubbles can detect female tumors precisely via dual-mode imaging in vivo. In conclusion, the new dual-mode IR-780-nanobubbles are stable and have potential advantages in non-invasive tumor-specific detection for female tumors via contrast-enhanced ultrasound and NIRF imaging.
authors.affiliation: Department of Ultrasound Diagnosis, Tang Du Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Hengli
authors.identifier: http://orcid.org/0000-0002-4938-3319
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Ultrasound Diagnosis, Tang Du Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Zhou
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 Urology, PLA 105 Hospital, Hefei, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Yi
authors.affiliation: Department of Ultrasound Diagnosis, Tang Du Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Ultrasound Diagnosis, Tang Du Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Yixiao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Ultrasound Diagnosis, Tang Du Hospital, Fourth Military Medical University, Xi'an, China. 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. duanyy@fmmu.edu.cn.
authors.forename: Yunyou
authors.initials: Y
authors.lastname: Duan
mesh_terms: D000818:Animals; D017209:Apoptosis; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D003287:Contrast Media; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007211:Indoles; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D014407:Tumor Cells, Cultured; D014463:Ultrasonography / Q000379:methods*; D023041:Xenograft Model Antitumor Assays
chemical_list: C548458:2-(2-(2-chloro-3-((1,3-dihydro-3,3-dimethyl-1-propyl-2H-indol-2-ylidene)ethylidene)-1-cyclohexen-1-yl)ethenyl)-3,3-dimethyl-1-propylindolium; D003287:Contrast Media; D007211:Indoles
keywords: Dual-mode; Female tumors; IR-780-nanobubbles; Tumor-specific