title: Microfluidic assembly of monodisperse, nanoparticle-incorporated perfluorocarbon microbubbles for medical imaging and therapy.
abstract: New medical imaging contrast agents that permit multiple imaging and therapy applications using a single agent can result in more accurate diagnosis and local treatment of diseased tissue. Solid nanoparticles (NPs) (5-150 nm in size) have emerged as promising imaging and therapy agents, as have micrometer-scale, perfluorocarbon gas-filled microbubbles (MBs) used in patients as intravascular ultrasound contrast agents. We propose that the modular combination of small, solid NPs and larger, highly compressible MBs into a single agent is an effective way to attain the desired complementary and hybrid properties of two very different agents. Presented here is a new strategy for the simple and robust incorporation of various medical NPs with monodisperse MBs based upon the controlled pH-based regulation of the electrostatic attraction between NPs and the MB shell. Using this simple approach, microfluidic-generated, protein-lipid-coated, perfluorobutane MBs (with size control down to 3 microm) were incorporated with silica-coated NPs, including CdSe/ZnS quantum dots, gold nanorods, iron oxide NPs, and Gd-loaded mesoporous silica NPs. The silica interface permits NP inclusion within MBs to be independent of NP composition, morphology, and size. Significantly, the NP-incorporated MBs (NP-MBs) diluted in saline were detectable using low-pressure ultrasound, and the monodisperse MB platform can be produced at high-throughput, sufficient for in vivo usage (10(6) MB/sec). The modular synthesis of a variety of NP-MBs can facilitate flexible, user-defined, multifunctional imaging and therapy agents tailored for specific applications and disease types.
authors.affiliation: Department of Medical Biophysics, University of Toronto, Ontario, Canada M4N 3M5.
authors.forename: Minseok
authors.initials: M
authors.lastname: Seo
authors.forename: Ivan
authors.initials: I
authors.lastname: Gorelikov
authors.forename: Ross
authors.initials: R
authors.lastname: Williams
authors.forename: Naomi
authors.initials: N
authors.lastname: Matsuura
mesh_terms: D003952:Diagnostic Imaging; D005466:Fluorocarbons / Q000737:chemistry* / Q000627:therapeutic use; D045423:Microbubbles; D044085:Microfluidics; D053758:Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use; D010316:Particle Size; D013499:Surface Properties
chemical_list: D005466:Fluorocarbons