"uuid","repository link","title","author","contributor","publication year","abstract","subject topic","language","publication type","publisher","isbn","issn","patent","patent status","bibliographic note","access restriction","embargo date","faculty","department","research group","programme","project","coordinates"
"uuid:90cdbd78-d2cb-451e-8b6d-58bbccae8cb6","http://resolver.tudelft.nl/uuid:90cdbd78-d2cb-451e-8b6d-58bbccae8cb6","Internalization of targeted microbubbles by endothelial cells and drug delivery by pores and tunnels","Beekers, Inés (Erasmus MC; Ortec B.V.); Langeveld, Simone A.G. (Erasmus MC); Meijlink, Bram (Erasmus MC); van der Steen, A.F.W. (Erasmus MC); de Jong, N. (TU Delft ImPhys/Medical Imaging; Erasmus MC); Verweij, M.D. (TU Delft ImPhys/Medical Imaging; Erasmus MC); Kooiman, Klazina (Erasmus MC)","","2022","Ultrasound insonification of microbubbles can locally enhance drug delivery by increasing the cell membrane permeability. To aid development of a safe and effective therapeutic microbubble, more insight into the microbubble-cell interaction is needed. In this in vitro study we aimed to investigate the initial 3D morphology of the endothelial cell membrane adjacent to individual microbubbles (n = 301), determine whether this morphology was affected upon binding and by the type of ligand on the microbubble, and study its influence on microbubble oscillation and the drug delivery outcome. High-resolution 3D confocal microscopy revealed that targeted microbubbles were internalized by endothelial cells, while this was not the case for non-targeted or IgG1-κ control microbubbles. The extent of internalization was ligand-dependent, since αvβ3-targeted microbubbles were significantly more internalized than CD31-targeted microbubbles. Ultra-high-speed imaging (~17 Mfps) in combination with high-resolution confocal microscopy (n = 246) showed that microbubble internalization resulted in a damped microbubble oscillation upon ultrasound insonification (2 MHz, 200 kPa peak negative pressure, 10 cycles). Despite damped oscillation, the cell's susceptibility to sonoporation (as indicated by PI uptake) was increased for internalized microbubbles. Monitoring cell membrane integrity (n = 230) showed the formation of either a pore, for intracellular delivery, or a tunnel (i.e. transcellular perforation), for transcellular delivery. Internalized microbubbles caused fewer transcellular perforations and smaller pore areas than non-internalized microbubbles. In conclusion, studying microbubble-mediated drug delivery using a state-of-the-art imaging system revealed receptor-mediated microbubble internalization and its effect on microbubble oscillation and resulting membrane perforation by pores and tunnels.","Drug delivery; Microbubbles; Sonoporation; Transcellular perforation; Ultrasound","en","journal article","","","","","","","","","","","ImPhys/Medical Imaging","","",""
"uuid:ee49615f-4786-43c7-ad06-edd18463c0e1","http://resolver.tudelft.nl/uuid:ee49615f-4786-43c7-ad06-edd18463c0e1","Opening of endothelial cell–cell contacts due to sonoporation","Beekers, D.I. (Erasmus MC); Vegter, Merel (Erasmus MC); Lattwein, Kirby R. (Erasmus MC); Mastik, Frits (Erasmus MC); Beurskens, Robert (Erasmus MC); van der Steen, A.F.W. (TU Delft ImPhys/Medical Imaging; Erasmus MC); de Jong, N. (TU Delft ImPhys/Medical Imaging; Erasmus MC); Verweij, M.D. (TU Delft ImPhys/Medical Imaging; Erasmus MC); Kooiman, Klazina (Erasmus MC)","","2020","Ultrasound insonification of microbubbles can locally increase vascular permeability to enhance drug delivery. To control and optimize the therapeutic potential, we need to better understand the underlying biological mechanisms of the drug delivery pathways. The aim of this in vitro study was to elucidate the microbubble-endothelial cell interaction using the Brandaris 128 ultra-high-speed camera (up to 25 Mfps) coupled to a custom-built Nikon confocal microscope, to visualize both microbubble oscillation and the cellular response. Sonoporation and opening of cell-cell contacts by single αVβ3-targeted microbubbles (n = 152) was monitored up to 4 min after ultrasound insonification (2 MHz, 100–400 kPa, 10 cycles). Sonoporation occurred when microbubble excursion amplitudes exceeded 0.7 μm. Quantification of the influx of the fluorescent model drug propidium iodide upon sonoporation showed that the size of the created pore increased for larger microbubble excursion amplitudes. Microbubble-mediated opening of cell-cell contacts occurred as a cellular response upon sonoporation and did not correlate with the microbubble excursion amplitude itself. The initial integrity of the cell-cell contacts affected the susceptibly to drug delivery, since cell-cell contacts opened more often when cells were only partially attached to their neighbors (48%) than when fully attached (14%). The drug delivery outcomes were independent of nonlinear microbubble behavior, microbubble location, and cell size. In conclusion, by studying the microbubble–cell interaction at nanosecond and nanometer resolution the relationship between drug delivery pathways and their underlying mechanisms was further unraveled. These novel insights will aid the development of safe and efficient microbubble-mediated drug delivery.","Cell-cell contact opening; Drug delivery; High-speed imaging; Microbubbles; Sonoporation; Ultrasound","en","journal article","","","","","","","","","","","ImPhys/Medical Imaging","","",""
"uuid:1c5db92d-95c4-40e0-ba73-ab140f72c6cd","http://resolver.tudelft.nl/uuid:1c5db92d-95c4-40e0-ba73-ab140f72c6cd","High-Resolution Imaging of Intracellular Calcium Fluctuations Caused by Oscillating Microbubbles","Beekers, D.I. (Erasmus MC); Mastik, Frits (Erasmus MC); Beurskens, Robert (Erasmus MC); Tang, Phoei Ying (Erasmus MC); Vegter, Merel (Erasmus MC); van der Steen, A.F.W. (TU Delft ImPhys/Medical Imaging; Erasmus MC); de Jong, N. (TU Delft ImPhys/Medical Imaging; Erasmus MC); Verweij, M.D. (TU Delft ImPhys/Medical Imaging; Erasmus MC); Kooiman, Klazina (Erasmus MC)","","2020","Ultrasound insonification of microbubbles can locally enhance drug delivery, but the microbubble–cell interaction remains poorly understood. Because intracellular calcium (Cai 2+) is a key cellular regulator, unraveling the Cai 2+ fluctuations caused by an oscillating microbubble provides crucial insight into the underlying bio-effects. Therefore, we developed an optical imaging system at nanometer and nanosecond resolution that can resolve Cai 2+ fluctuations and microbubble oscillations. Using this system, we clearly distinguished three Cai 2+ uptake profiles upon sonoporation of endothelial cells, which strongly correlated with the microbubble oscillation amplitude, severity of sonoporation and opening of cell–cell contacts. We found a narrow operating range for viable drug delivery without lethal cell damage. Moreover, adjacent cells were affected by a calcium wave propagating at 15 μm/s. With the unique optical system, we unraveled the microbubble oscillation behavior required for drug delivery and Cai 2+ fluctuations, providing new insight into the microbubble–cell interaction to aid clinical translation.","Cell–cell contact opening; Confocal microscopy; Drug delivery; High-speed imaging; Intracellular calcium; Microbubbles; Sonoporation; Ultrasound","en","journal article","","","","","","","","","","","ImPhys/Medical Imaging","","",""
"uuid:3d2f11ed-294e-40d9-9ed6-a102967dd402","http://resolver.tudelft.nl/uuid:3d2f11ed-294e-40d9-9ed6-a102967dd402","Laser-driven resonance of dye-doped oil-coated microbubbles: Experimental study","Lajoinie, Guillaume (University of Twente); Lee, Jeong Yu (University of Oxford); Owen, Joshua (University of Oxford); Kruizinga, P. (TU Delft ImPhys/Acoustical Wavefield Imaging; Erasmus MC); de Jong, N. (TU Delft ImPhys/Acoustical Wavefield Imaging; Erasmus MC); Van Soest, Gijs (Erasmus MC); Stride, Eleanor (University of Oxford); Versluis, Michel (University of Twente)","","2017","Photoacoustic (PA) imaging offers several attractive features as a biomedical imaging modality, including excellent spatial resolution and functional information such as tissue oxygenation. A key limitation, however, is the contrast to noise ratio that can be obtained from tissue depths greater than 1-2 mm. Microbubbles coated with an optically absorbing shell have been proposed as a possible contrast agent for PA imaging, offering greater signal amplification and improved biocompatibility compared to metallic nanoparticles. A theoretical description of the dynamics of a coated microbubble subject to laser irradiation has been developed previously. The aim of this study was to test the predictions of the model. Two different types of oil-coated microbubbles were fabricated and then exposed to both pulsed and continuous wave (CW) laser irradiation. Their response was characterized using ultra high-speed imaging. Although there was considerable variability across the population, good agreement was found between the experimental results and theoretical predictions in terms of the frequency and amplitude of microbubble oscillation following pulsed excitation. Under CW irradiation, highly nonlinear behavior was observed which may be of considerable interest for developing different PA imaging techniques with greatly improved contrast enhancement.","Lasers; Microbubbles; Acoustic signal processing; Medical imaging; Acoustic transducers","en","journal article","","","","","","","","","","","ImPhys/Acoustical Wavefield Imaging","","",""
"uuid:31bce0f8-c532-4264-8caf-155f4eda537d","http://resolver.tudelft.nl/uuid:31bce0f8-c532-4264-8caf-155f4eda537d","Development of a new therapeutic technique to direct stem cells to the infarcted heart using targeted microbubbles: StemBells","Woudstra, L. (Amsterdam UMC); Krijnen, PAJ (Amsterdam UMC); Bogaards, SJP (Amsterdam UMC); Meinster, E (Amsterdam UMC); Emmens, RW (Amsterdam UMC; Erasmus MC); Kokhuis, TJA (Interuniversity Cardiology Institute of the Netherlands (ICIN)); Bollen, IAE (Amsterdam UMC); Baltzer, H (Amsterdam UMC); Baart, SMT (Amsterdam UMC); Parbhudayal, R (Amsterdam UMC); de Jong, N. (TU Delft ImPhys/Acoustical Wavefield Imaging; Erasmus MC; Interuniversity Cardiology Institute of the Netherlands (ICIN)); Helder, MN (Amsterdam UMC); Hinsbergh, V.W.M. (Amsterdam UMC); Musters, RJP (Amsterdam UMC); Kamp, O. (Interuniversity Cardiology Institute of the Netherlands (ICIN); Amsterdam UMC); Niessen, H.W.M. (Amsterdam UMC); van Dijk, A. (Amsterdam UMC); Juffermans, LJ (Amsterdam UMC; Interuniversity Cardiology Institute of the Netherlands (ICIN))","","2016","Successful stem cell therapy after acute myocardial infarction (AMI) is hindered by lack of engraftment of sufficient stem cells at the site of injury. We designed a novel technique to overcome this problem by assembling stem cell-microbubble complexes, named 'StemBells'. StemBells were assembled through binding of dual-targeted microbubbles (~3μm) to adipose-derived stem cells (ASCs) via a CD90 antibody. StemBells were targeted to the infarct area via an ICAM-1 antibody on the microbubbles. StemBells were characterized microscopically and by flow cytometry. The effect of ultrasound on directing StemBells towards the vessel wall was demonstrated in an in vitro flow model. In a rat AMI-reperfusion model, StemBells or ASCs were injected one week post-infarction. A pilot study demonstrated feasibility of intravenous StemBell injection, resulting in localization in ICAM-1-positive infarct area three hours post-injection. In a functional study five weeks after injection of StemBells cardiac function was significantly improved compared with controls, as monitored by 2D-echocardiography. This functional improvement neither coincided with a reduction in infarct size as determined by histochemical analysis, nor with a change in anti- and pro-inflammatory macrophages. In conclusion, the StemBell technique is a novel and feasible method, able to improve cardiac function post-AMI in rats.","Acoustic radiation force; Acute myocardial infarction; Adipose tissue-derived stem cells; Microbubbles; StemBells; Targeting","en","journal article","","","","","","","","","","","ImPhys/Acoustical Wavefield Imaging","","",""