Nanoparticle-stabilized microbubbles for multimodal imaging and drug delivery.
Microbubbles (MBs) are routinely used as contrast agents for ultrasound imaging. The use of ultrasound in combination with MBs has also attracted attention as a method to enhance drug delivery. We have developed a technology platform incorporating multiple functionalities, including imaging and therapy in a single system consisting of MBs stabilized by polyethylene glycol (PEG)-coated polymeric nanoparticles (NPs). The NPs, containing lipophilic drugs and/or contrast agents, are composed of the widely used poly(butyl cyanoacrylate) (PBCA) polymer and prepared in a single step. MBs stabilized by these NPs are subsequently prepared by self-assembly of NPs at the MB air-liquid interface. Here we show that these MBs can act as contrast agents for conventional ultrasound imaging. Successful encapsulation of iron oxide NPs inside the PBCA NPs is demonstrated, potentially enabling the NP-MBs to be used as magnetic resonance imaging (MRI) and/or molecular ultrasound imaging contrast agents. By precise tuning of the applied ultrasound pulse, the MBs burst and the NPs constituting the shell are released. This could result in increased local deposit of NPs into target tissue, providing improved therapy and imaging contrast compared with freely distributed NPs.
SINTEF Materials and Chemistry, P.O. Box 4760 Sluppen, 7465, Trondheim, Norway.
Ýrr
Ý
Mørch
SINTEF Technology and Society, P.O. Box 4760 Sluppen, 7465, Trondheim, Norway.
Rune
R
Hansen
SINTEF Technology and Society, P.O. Box 4760 Sluppen, 7465, Trondheim, Norway.
Sigrid
S
Berg
Department of Physics, Norwegian University of Science and Technology, 7491, Trondheim, Norway.
Andreas K O
AK
Åslund
SINTEF Materials and Chemistry, P.O. Box 4760 Sluppen, 7465, Trondheim, Norway.|Department of Chemical Engineering, Norwegian University of Science and Technology, 7491, Trondheim, Norway.
Wilhelm R
WR
Glomm
Department of Physics, Norwegian University of Science and Technology, 7491, Trondheim, Norway.
Siv
S
Eggen
SINTEF Materials and Chemistry, P.O. Box 4760 Sluppen, 7465, Trondheim, Norway.
Ruth
R
Schmid
SINTEF Materials and Chemistry, P.O. Box 4760 Sluppen, 7465, Trondheim, Norway.
Heidi
H
Johnsen
SINTEF Materials and Chemistry, P.O. Box 4760 Sluppen, 7465, Trondheim, Norway.
Stephan
S
Kubowicz
Department of Physics, Norwegian University of Science and Technology, 7491, Trondheim, Norway.
Sofie
S
Snipstad
Department of Physics, Norwegian University of Science and Technology, 7491, Trondheim, Norway.
Einar
E
Sulheim
Department of Physics, Norwegian University of Science and Technology, 7491, Trondheim, Norway.|Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, 7030, Trondheim, Norway.
Sjoerd
S
Hak
Department of Chemical Engineering, Norwegian University of Science and Technology, 7491, Trondheim, Norway.
Gurvinder
G
Singh
Department of Chemical Engineering, Norwegian University of Science and Technology, 7491, Trondheim, Norway.
Birgitte H
BH
McDonagh
Science for Life Laboratory, Box 1031, 17121, Solna, Sweden.
Hans
H
Blom
Department of Physics, Norwegian University of Science and Technology, 7491, Trondheim, Norway.
Catharina
C
de Lange Davies
SINTEF Materials and Chemistry, P.O. Box 4760 Sluppen, 7465, Trondheim, Norway.
Per M
PM
Stenstad
D016503:Drug Delivery Systems / Q000379:methods*; D004659:Enbucrilate / Q000737:chemistry*; D045423:Microbubbles; D064847:Multimodal Imaging / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*
D011108:Polymers; D004659:Enbucrilate
focused ultrasound; microbubble; nanoparticle; poly(butyl cyanoacrylate); targeted drug delivery; theranostics