Mechanical and dynamic characteristics of encapsulated microbubbles coupled by magnetic nanoparticles as multifunctional imaging and drug delivery agents

• Published in: Physics in medicine & biology Vol. 59; no. 22; pp. 6729 - 6747
• Main Authors: Guo, Gepu, Lu, Lu, Yin, Leilei, Tu, Juan, Guo, Xiasheng, Wu, Junru, Xu, Di, Zhang, Dong
• Format: Journal Article
• Language: English
• Published: England IOP Publishing 21.11.2014
• Subjects: Acoustics; Albumins - chemistry; atomic force microscopy; Cell Survival; Contrast Media - chemistry; Drug Delivery Systems; Enzyme-Linked Immunosorbent Assay; Ferric Compounds - chemistry; Fluorocarbons - chemistry; gene/drug delivery; HEK293 Cells; Humans; inertial cavitation; magnetic nanoparticles; Magnetic Resonance Imaging; Magnetite Nanoparticles - chemistry; Microbubbles; Microscopy, Atomic Force; Microscopy, Electron, Scanning; multifunctional contrast agent microbubbles; Multimodal Imaging - methods; Nanotechnology - methods; Phantoms, Imaging; Ultrasonics - methods; ultrasound imaging; Vascular Endothelial Growth Factor A - metabolism
• ISSN: 0031-9155; 1361-6560; 1361-6560
• DOI: 10.1088/0031-9155/59/22/6729

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.