Ultrasound-enhanced drug delivery in prostate cancer xenografts by nanoparticles stabilizing microbubbles.
The delivery of nanoparticles to solid tumors is often ineffective due to the lack of specificity towards tumor tissue, limited transportation of the nanoparticles across the vascular wall and poor penetration through the extracellular matrix of the tumor. Ultrasound is a promising tool that can potentially improve several of the transportation steps, and the interaction between sound waves and microbubbles generates biological effects that can be beneficial for the successful delivery of nanocarriers and their contents. In this study, a novel platform consisting of nanoparticle-stabilized microbubbles has been investigated for its potential for ultrasound-enhanced delivery to tumor xenografts. Confocal laser scanning microscopy was used to study the supply of nanoparticles from the vasculature and to evaluate the effect of different ultrasound parameters at a microscopic level. The results demonstrated that although the delivery is heterogeneous within tumors, there is a significant improvement in the delivery and the microscopic distribution of both nanoparticles and a released model drug when the nanoparticles are combined with microbubbles and ultrasound. The mechanisms that underlie the improved delivery are discussed.
Department of Physics, Norwegian University of Science and Technology, Trondheim, Norway. Electronic address: siv.eggen@ntnu.no.
Siv
S
Eggen
Department of Physics, Norwegian University of Science and Technology, Trondheim, Norway.
Stein-Martin
SM
Fagerland
SINTEF Materials and Chemistry, Dept. of Polymer Particles and Surface Chemistry, Trondheim, Norway.
Ýrr
Ý
Mørch
SINTEF Technology and Society, Dept. of Medical Technology, Trondheim, Norway; Department of Circulation and Diagnostic Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
Rune
R
Hansen
Department of Physics, Norwegian University of Science and Technology, Trondheim, Norway.
Kishia
K
Søvik
SINTEF Technology and Society, Dept. of Medical Technology, Trondheim, Norway.
Sigrid
S
Berg
Department of Physics, Norwegian University of Science and Technology, Trondheim, Norway.
Håkon
H
Furu
Department of Physics, Norwegian University of Science and Technology, Trondheim, Norway.
Audun Dybvik
AD
Bøhn
Department of Physics, Norwegian University of Science and Technology, Trondheim, Norway.
Magnus B
MB
Lilledahl
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway; Department of Urological Surgery, St. Olavs Hospital, Trondheim University Hospital, Norway.
Anders
A
Angelsen
Department of Circulation and Diagnostic Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
Bjørn
B
Angelsen
Department of Physics, Norwegian University of Science and Technology, Trondheim, Norway.
Catharina
C
de Lange Davies
D000818:Animals; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D004659:Enbucrilate / Q000737:chemistry; D064593:Heterografts / Q000378:metabolism; D006801:Humans; D008297:Male; D008819:Mice, Nude; D045423:Microbubbles; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000378:metabolism*; D014465:Ultrasonics
D011092:Polyethylene Glycols; D004659:Enbucrilate
Drug delivery; Microbubbles; Microdistribution; Nanoparticles; Solid tumor; Ultrasound