title: Controlled assembly of magnetic nanoparticles on microbubbles for multimodal imaging.
abstract: Magnetic microbubbles (MMBs) consisting of microbubbles (MBs) and magnetic nanoparticles (MNPs) were synthesized for use as novel markers for improving multifunctional biomedical imaging. The MMBs were fabricated by assembling MNPs in different concentrations on the surfaces of MBs. The relationships between the structure, magnetic properties, stability of the MMBs, and their use in magnetic resonance/ultrasound (MR/US) dual imaging applications were determined. The MNPs used were NPs of 3-aminopropyltriethoxysilane (APTS)-functionalized superparamagnetic iron oxide γ-Fe2O3 (SPIO). SPIO was assembled on the surfaces of polymer MBs using a "surface-coating" approach. An analysis of the underlying mechanism showed that the synergistic effects of covalent coupling, electrostatic adsorption, and aggregation of the MNPs allowed them to be unevenly assembled in large amounts on the surfaces of the MBs. With an increase in the MNP loading amount, the magnetic properties of the MMBs improved significantly; in this way, the shell structure and mechanical properties of the MMBs could be modified. For surface densities ranging from 2.45 × 10(-7) μg per MMB to 8.45 × 10(-7) μg per MMB, in vitro MR/US imaging experiments showed that, with an increase in the number of MNPs on the surfaces of the MBs, the MMBs exhibited better T2 MR imaging contrast, as well as an increase in the US contrast for longer durations. In vivo experiments also showed that, by optimizing the structure of the MMBs, enhanced MR/US dual-modality image signals could be obtained for mouse tumors. Therefore, by adjusting the shell composition of MBs through the assembly of MNPs in different concentrations, MMBs with good magnetic and acoustic properties for MR/US dual-modality imaging contrast agents could be obtained.
authors.affiliation: State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, P. R. China. guning@seu.edu.cn.
authors.forename: Lei
authors.initials: L
authors.lastname: Duan
authors.forename: Fang
authors.initials: F
authors.lastname: Yang
authors.forename: Lina
authors.initials: L
authors.lastname: Song
authors.forename: Kun
authors.initials: K
authors.lastname: Fang
authors.forename: Jilai
authors.initials: J
authors.lastname: Tian
authors.forename: Yijun
authors.initials: Y
authors.lastname: Liang
authors.forename: Mingxi
authors.initials: M
authors.lastname: Li
authors.forename: Ning
authors.initials: N
authors.lastname: Xu
authors.forename: Zhongda
authors.initials: Z
authors.lastname: Chen
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ning
authors.initials: N
authors.lastname: Gu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000138:chemical synthesis*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D045423:Microbubbles; D064847:Multimodal Imaging; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging*; D010316:Particle Size; D011437:Propylamines; D012821:Silanes / Q000737:chemistry; D013499:Surface Properties; D014463:Ultrasonography
chemical_list: D003287:Contrast Media; D058185:Magnetite Nanoparticles; D011437:Propylamines; D012821:Silanes; C477625:amino-propyl-triethoxysilane