title: Mechanical and dynamic characteristics of encapsulated microbubbles coupled by magnetic nanoparticles as multifunctional imaging and drug delivery agents.
abstract: Development of magnetic encapsulated microbubble agents that can integrate multiple diagnostic and therapeutic functions is a key focus in both biomedical engineering and nanotechnology and one which will have far-reaching impact on medical diagnosis and therapies. However, properly designing multifunctional agents that can satisfy particular diagnostic/therapeutic requirements has been recognized as rather challenging, because there is a lack of comprehensive understanding of how the integration of magnetic nanoparticles to microbubble encapsulating shells affects their mechanical properties and dynamic performance in ultrasound imaging and drug delivery. Here, a multifunctional imaging contrast and in-situ gene/drug delivery agent was synthesized by coupling super paramagnetic iron oxide nanoparticles (SPIOs) into albumin-shelled microbubbles. Systematical studies were performed to investigate the SPIO-concentration-dependence of microbubble mechanical properties, acoustic scattering response, inertial cavitation activity and ultrasound-facilitated gene transfection effect. These demonstrated that, with the increasing SPIO concentration, the microbubble mean diameter and shell stiffness increased and ultrasound scattering response and inertial cavitation activity could be significantly enhanced. However, an optimized ultrasound-facilitated vascular endothelial growth factor transfection outcome would be achieved by adopting magnetic albumin-shelled microbubbles with an appropriate SPIO concentration of 114.7 µg ml(-1). The current results would provide helpful guidance for future development of multifunctional agents and further optimization of their diagnostic/therapeutic performance in clinic.
authors.affiliation: Key Laboratory of Modern Acoustics (MOE), Institute of Acoustics, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Gepu
authors.initials: G
authors.lastname: Guo
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.forename: Leilei
authors.initials: L
authors.lastname: Yin
authors.forename: Juan
authors.initials: J
authors.lastname: Tu
authors.forename: Xiasheng
authors.initials: X
authors.lastname: Guo
authors.forename: Junru
authors.initials: J
authors.lastname: Wu
authors.forename: Di
authors.initials: D
authors.lastname: Xu
authors.forename: Dong
authors.initials: D
authors.lastname: Zhang
mesh_terms: D000162:Acoustics; D000418:Albumins / Q000737:chemistry; D002470:Cell Survival; D003287:Contrast Media / Q000737:chemistry*; D016503:Drug Delivery Systems; D004797:Enzyme-Linked Immunosorbent Assay; D005290:Ferric Compounds / Q000737:chemistry; D005466:Fluorocarbons / Q000737:chemistry; D057809:HEK293 Cells; D006801:Humans; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D045423:Microbubbles; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D064847:Multimodal Imaging / Q000379:methods*; D036103:Nanotechnology / Q000379:methods; D019047:Phantoms, Imaging; D014465:Ultrasonics / Q000379:methods; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D000418:Albumins; D003287:Contrast Media; D005290:Ferric Compounds; D005466:Fluorocarbons; D058185:Magnetite Nanoparticles; D042461:Vascular Endothelial Growth Factor A; C000499:ferric oxide