A versatile method for the preparation of particle-loaded microbubbles for multimodality imaging and targeted drug delivery

Abstract

Microbubbles are currently in clinical use as ultrasound contrast agents and under active investigation as mediators of ultrasound therapy. To improve the theranostic potential of microbubbles, nanoparticles can be attached to the bubble shell for imaging, targeting and/or enhancement of acoustic response. Existing methods for fabricating particle-loaded bubbles, however, require the use of polymers, oil layers or chemical reactions for particle incorporation; embed/attach the particles that can reduce echogenicity; impair biocompatibility; and/or involve multiple processing steps. Here, we describe a simple method to embed nanoparticles in a phospholipid-coated microbubble formulation that overcomes these limitations. Magnetic nanoparticles are used to demonstrate the method with a range of different microbubble formulations. The size distribution and yield of microbubbles are shown to be unaffected by the addition of the particles. We further show that the microbubbles can be retained against flow using a permanent magnet, can be visualised by both ultrasound and magnetic resonance imaging (MRI) and can be used to transfect SH-SY5Y cells with fluorescent small interfering RNA under the application of a magnetic field and ultrasound field.Electronic supplementary materialThe online version of this article (doi:10.1007/s13346-017-0366-7) contains supplementary material, which is available to authorized users.

Ultrasound‐mediated therapies for the treatment of biofilms in chronic wounds: a review of present knowledge

“…The architecture of gas-filled microbubbles is variable according to their intended application, though they commonly consist of a surfactant, polymer, protein or phospholipid shell, which encapsulates a gaseous core ( Fig. 2) (Sirsi and Borden, 2009;Owen et al, 2018). The composition of the MB shell is integral to conferring mechanical stability, preventing coalescence and determining its acoustic response to stimulation by ultrasound (US) (Borden et al, 2005;Stride, 2008;Carugo et al, 2017).…”

Nano Meets Micro-Translational Nanotechnology in Medicine: Nano-Based Applications for Early Tumor Detection and Therapy

“…Multiple hybrid MBs are also being developed that carry NPs enclosed in or attached to their shell, including superparamagnetic iron oxides [128,129], QDs [130], gold clusters or nanorods [102,131,132], GO sheets [133], cerium oxide NPs [134], liposomes [135]. Small and stable MBs decorated with dendronized iron oxide magnetic NPs were obtained that are stabilized by fluorine-fluorine interactions between the internal FC gas and the fluorinated terminal end-group of the oligo(ethylene glycol)-based dendrons [136].…”

Microbubbles decorated with dendronized magnetic nanoparticles for biomedical imaging: effective stabilization via fluorous interactions

“…One important difficulty encountered in the preparation of such magnetic MBs is that IONPs rapidly aggregate in aqueous media [25]. Commercially available 50 nm magnetic IONPs coated with phospholipids allowed for the preparation of MBs that enabled transfection of neuroblastoma cells with a generic, fluorescent, small, interfering RNA under magnetic and ultrasound fields [26].…”