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196 results on '"Davies, Catharina de Lange"'

3. Ultrasound enhanced diffusion in hydrogels: An experimental and non-equilibrium molecular dynamics study.

Author

Price, Sebastian E. N., Einen, Caroline, Moultos, Othonas A., Vlugt, Thijs J. H., Davies, Catharina de Lange, Eiser, Erika, and Lervik, Anders

Subjects
MOLECULAR dynamics, ULTRASONIC imaging, HEAT equation, RANDOM walks, DIFFUSION coefficients, HYDROGELS, NON-equilibrium reactions
Abstract

Focused ultrasound has experimentally been found to enhance the diffusion of nanoparticles; our aim with this work is to study this effect closer using both experiments and non-equilibrium molecular dynamics. Measurements from single particle tracking of 40 nm polystyrene nanoparticles in an agarose hydrogel with and without focused ultrasound are presented and compared with a previous experimental study using 100 nm polystyrene nanoparticles. In both cases, we observed an increase in the mean square displacement during focused ultrasound treatment. We developed a coarse-grained non-equilibrium molecular dynamics model with an implicit solvent to investigate the increase in the mean square displacement and its frequency and amplitude dependencies. This model consists of polymer fibers and two sizes of nanoparticles, and the effect of the focused ultrasound was modeled as an external oscillating force field. A comparison between the simulation and experimental results shows similar mean square displacement trends, suggesting that the particle velocity is a significant contributor to the observed ultrasound-enhanced mean square displacement. The resulting diffusion coefficients from the model are compared to the diffusion equation for a two-time continuous time random walk. The model is found to have the same frequency dependency. At lower particle velocity amplitude values, the model has a quadratic relation with the particle velocity amplitude as described by the two-time continuous time random walk derived diffusion equation, but at higher amplitudes, the model deviates, and its diffusion coefficient reaches the non-hindered diffusion coefficient. This observation suggests that at higher ultrasound intensities in hydrogels, the non-hindered diffusion coefficient can be used. [ABSTRACT FROM AUTHOR]

Published
2024
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15. A Comparative Analysis of Orthotopic and Subcutaneous Pancreatic Tumour Models: Tumour Microenvironment and Drug Delivery

Author

Fernandez, Jessica Lage, primary, Årbogen, Sara, additional, Sadeghinia, Mohammad Javad, additional, Haram, Margrete, additional, Snipstad, Sofie, additional, Torp, Sverre Helge, additional, Einen, Caroline, additional, Mühlenpfordt, Melina, additional, Maardalen, Matilde, additional, Vikedal, Krister, additional, and Davies, Catharina de Lange, additional

Published
2023
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19. Contrast Enhanced Magnetic Resonance Imaging of Amyloid-beta Plaques in a Murine Alzheimers Disease Model

Author

Sulheim, Einar, Wideroe, Marius, Bäck, Marcus, Nilsson, Peter, Hammarström, Per, Nilsson, Lars N. G., Davies, Catharina de Lange, Aslund, Andreas K. O., Sulheim, Einar, Wideroe, Marius, Bäck, Marcus, Nilsson, Peter, Hammarström, Per, Nilsson, Lars N. G., Davies, Catharina de Lange, and Aslund, Andreas K. O.

Abstract

Background: Early detection of amyloid-beta(A beta) aggregates is a critical step to improve the treatment of Alzheimers disease (AD) because neuronal damage by the A beta aggregates occurs before clinical symptoms are apparent. We have previously shown that luminescent conjugated oligothiophenes (LCOs), which are highly specific towards protein aggregates of A beta, can be used to fluorescently label amyloid plaque in living rodents. Objective: We hypothesize that the LCO can be used to target gadolinium to the amyloid plaque and hence make the plaque detectable by T-1-weighted magnetic resonance imaging (MRI). Methods: A novel LCO-gadolinium construct was synthesized to selectively bind to A beta plaques and give contrast in conventional T-1-weighted MR images after intravenous injection in Tg-APPSwe mice. Results: We found that mice with high plaque-burden could be identified using the LCO-Gd constructs by conventional MRI. Conclusion: Our study shows that MR imaging of amyloid plaques is challenging but feasible, and hence contrast-mediated MR imaging could be a valuable tool for early AD detection., Funding Agencies|Central Norway Regional Health Authority [46084000]; Research Council of Norway [240316]; Swedish Research Council [2016-00748]

Published
2023
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24. Inflammatory Lesions: Cyclic Arginine–Glycine–Aspartate‐Decorated Lipid Nanoparticle Targeting toward Inflammatory Lesions Involves Hitchhiking with Phagocytes (Adv. Sci. 13/2021)

Author

Sofias, Alexandros Marios, primary, Bjørkøy, Geir, additional, Ochando, Jordi, additional, Sønstevold, Linda, additional, Hegvik, Maria, additional, Davies, Catharina de Lange, additional, Haraldseth, Olav, additional, Lammers, Twan, additional, Mulder, Willem J. M., additional, and Hak, Sjoerd, additional

Published
2021
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25. Cyclic Arginine–Glycine–Aspartate‐Decorated Lipid Nanoparticle Targeting toward Inflammatory Lesions Involves Hitchhiking with Phagocytes

Author

Sofias, Alexandros Marios, primary, Bjørkøy, Geir, additional, Ochando, Jordi, additional, Sønstevold, Linda, additional, Hegvik, Maria, additional, Davies, Catharina de Lange, additional, Haraldseth, Olav, additional, Lammers, Twan, additional, Mulder, Willem J. M., additional, and Hak, Sjoerd, additional

Published
2021
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26. Tumor Targeting by αvβ3-Integrin-Specific Lipid Nanoparticles Occurs via Phagocyte Hitchhiking

Author

Sofias, Alexandros Marios, primary, Toner, Yohana C., additional, Meerwaldt, Anu E., additional, van Leent, Mandy M. T., additional, Soultanidis, Georgios, additional, Elschot, Mattijs, additional, Gonai, Haruki, additional, Grendstad, Kristin, additional, Flobak, Åsmund, additional, Neckmann, Ulrike, additional, Wolowczyk, Camilla, additional, Fisher, Elizabeth L., additional, Reiner, Thomas, additional, Davies, Catharina de Lange, additional, Bjørkøy, Geir, additional, Teunissen, Abraham J. P., additional, Ochando, Jordi, additional, Pérez-Medina, Carlos, additional, Mulder, Willem J. M., additional, and Hak, Sjoerd, additional

Published
2020
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27. Theranostic Attributes of Acoustic Cluster Therapy and Its Use for Enhancing the Effectiveness of Liposomal Doxorubicin Treatment of Human Triple Negative Breast Cancer in Mice

Author

Bush, Nigel, primary, Healey, Andrew, additional, Shah, Anant, additional, Box, Gary, additional, Kirkin, Vladimir, additional, Eccles, Sue, additional, Sontum, Per Christian, additional, Kotopoulis, Spiros, additional, Kvåle, Svein, additional, van Wamel, Annemieke, additional, Davies, Catharina de Lange, additional, and Bamber, Jeffrey, additional

Published
2020
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30. Tumor Targeting by αvβ3‑Integrin-Specific Lipid Nanoparticles Occurs via Phagocyte Hitchhiking.

Author

Sofias, Alexandros Marios, Toner, Yohana C., Meerwaldt, Anu E., van Leent, Mandy M. T., Soultanidis, Georgios, Elschot, Mattijs, Gonai, Haruki, Grendstad, Kristin, Flobak, Åsmund, Neckmann, Ulrike, Wolowczyk, Camilla, Fisher, Elizabeth L., Reiner, Thomas, Davies, Catharina de Lange, Bjørkøy, Geir, Teunissen, Abraham J. P., Ochando, Jordi, Pérez-Medina, Carlos, Mulder, Willem J. M., and Hak, Sjoerd

Published
2020
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35. Quantification and Qualitative Effects of Different PEGylations on Poly(butyl cyanoacrylate) Nanoparticles

Author

Åslund, Andreas K. O., primary, Sulheim, Einar, additional, Snipstad, Sofie, additional, von Haartman, Eva, additional, Baghirov, Habib, additional, Starr, Nichola, additional, Kvåle Løvmo, Mia, additional, Lelú, Sylvie, additional, Scurr, David, additional, Davies, Catharina de Lange, additional, Schmid, Ruth, additional, and Mørch, Ýrr, additional

Published
2017
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37. Single Cell Confocal Raman Spectroscopy of Human Osteoarthritic Chondrocytes: A Preliminary Study

Author

Kumar, Rajesh, Singh, Gajendra, Grønhaug, Kirsten, Afseth, Nils, Davies, Catharina de Lange, Drogset, Jon, Lilledahl, Magnus, Massachusetts Institute of Technology. Research Laboratory of Electronics, and Singh, Gajendra Pratap

Subjects
osteoarthritis, Raman spectroscopy, chondrocytes, biomedical optical diagnosis
Abstract

A great deal of effort has been focused on exploring the underlying molecular mechanism of osteoarthritis (OA) especially at the cellular level. We report a confocal Raman spectroscopic investigation on human osteoarthritic chondrocytes. The objective of this investigation is to identify molecular features and the stage of OA based on the spectral signatures corresponding to bio-molecular changes at the cellular level in chondrocytes. In this study, we isolated chondrocytes from human osteoarthritic cartilage and acquired Raman spectra from single cells. Major spectral differences between the cells obtained from different International Cartilage Repair Society (ICRS) grades of osteoarthritic cartilage were identified. During progression of OA, a decrease in protein content and an increase in cell death were observed from the vibrational spectra. Principal component analysis and subsequent cross-validation was able to associate osteoarthritic chondrocytes to ICRS Grade I, II and III with specificity 100.0%, 98.1%, and 90.7% respectively, while, sensitivity was 98.6%, 82.8%, and 97.5% respectively. The overall predictive efficiency was 92.2%. Our pilot study encourages further use of Raman spectroscopy as a noninvasive and label free technique for revealing molecular features associated with osteoarthritic chondrocytes., Norwegian University of Science and Technology

Published
2015

39. Tumor Targeting by αvβ3-Integrin-Specific Lipid Nanoparticles Occurs viaPhagocyte Hitchhiking

Author

Sofias, Alexandros Marios, Toner, Yohana C., Meerwaldt, Anu E., van Leent, Mandy M. T., Soultanidis, Georgios, Elschot, Mattijs, Gonai, Haruki, Grendstad, Kristin, Flobak, Åsmund, Neckmann, Ulrike, Wolowczyk, Camilla, Fisher, Elizabeth L., Reiner, Thomas, Davies, Catharina de Lange, Bjørkøy, Geir, Teunissen, Abraham J. P., Ochando, Jordi, Pérez-Medina, Carlos, Mulder, Willem J. M., and Hak, Sjoerd

Abstract

Although the first nanomedicine was clinically approved more than two decades ago, nanoparticles’ (NP) in vivobehavior is complex and the immune system’s role in their application remains elusive. At present, only passive-targeting nanoformulations have been clinically approved, while more complicated active-targeting strategies typically fail to advance from the early clinical phase stage. This absence of clinical translation is, among others, due to the very limited understanding for in vivotargeting mechanisms. Dynamic in vivophenomena such as NPs’ real-time targeting kinetics and phagocytes’ contribution to active NP targeting remain largely unexplored. To better understand in vivotargeting, monitoring NP accumulation and distribution at complementary levels of spatial and temporal resolution is imperative. Here, we integrate in vivopositron emission tomography/computed tomography imaging with intravital microscopy and flow cytometric analyses to study αvβ3-integrin-targeted cyclic arginine-glycine-aspartate decorated liposomes and oil-in-water nanoemulsions in tumor mouse models. We observed that ligand-mediated accumulation in cancerous lesions is multifaceted and identified “NP hitchhiking” with phagocytes to contribute considerably to this intricate process. We anticipate that this understanding can facilitate rational improvement of nanomedicine applications and that immune cell–NP interactions can be harnessed to develop clinically viable nanomedicine-based immunotherapies.

Published
2020
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40. Near-Infrared Fluorescence Energy Transfer Imaging of Nanoparticle Accumulation and Dissociation Kinetics in Tumor-Bearing Mice

Author

Zhao, Yiming, van Rooy, Inge, Hak, Sjoerd, Fay, Francois, Tang, Jun, Davies, Catharina de Lange, Skobe, Mihaela, Fisher, Edward Allen, Radu, Aurelian, Fayad, Zahi. A., de Mello Donegá, Celso, Meijerink, Andries, and Mulder, Willem J. M.

Abstract

In the current study we show the dissociation and tumor accumulation dynamics of dual-labeled near-infrared quantum dot core self-assembled lipidic nanoparticles (SALNPs) in a mouse model upon intravenous administration. Using advanced in vivofluorescence energy transfer imaging techniques, we observed swift exchange with plasma protein components in the blood and progressive SALNP dissociation and subsequent trafficking of individual SALNP components following tumor accumulation. Our results suggest that upon intravenous administration SALNPs quickly transform, which may affect their functionality. The presented technology provides a modular in vivotool to visualize SALNP behavior in real time and may contribute to improving the therapeutic outcome or molecular imaging signature of SALNPs.

Published
2024
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42. Contact-mediated intracellular delivery of hydrophobic drugs from polymeric nanoparticles

Author

Snipstad, Sofie, Westrøm, Sara, Mørch, Ýrr Asbjørg, Afadzi, Mercy, Åslund, Andreas, and Davies, Catharina De Lange

Abstract

Encapsulation of drugs in nanoparticles can enhance the accumulation of drugs in tumours, reduce toxicity toward healthy tissue, and improve pharmacokinetics compared to administration of free drug. To achieve efficient delivery and release of drugs at the target site, mechanisms of interaction between the nanoparticles and cells and the mechanism of delivery of the encapsulated drug are crucial to understand. Our aim was to determine the mechanisms for cellular uptake of a fluorescent hydrophobic model drug from poly(butylcyanoacrylate) nanoparticles. Prostate adenocarcinoma cells were incubated with Nile Red-loaded nanoparticles or free Nile Red. Uptake and intracellular distribution were evaluated by flow cytometry and confocal laser scanning microscopy. The nanoparticles mediated a higher intracellular level and more rapid uptake of encapsulated Nile Red compared to model drug administered alone. The main mechanism for delivery was not by endocytosis of nanoparticles but by nanoparticle-cell contact-mediated transfer directly to the cytosol and, to a smaller extent, release of payload from nanoparticles into the medium followed by diffusion into cells. The payload thus avoids entering the endocytic pathway, evading lysosomal degradation and instead gains direct access to intracellular targets. The nanoparticles are promising tools for efficient intracellular delivery of hydrophobic anticancer drugs; therefore, they are clinically relevant for improved cancer therapy. © Snipstad et al.; licensee Springer. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://​creativecommons.​org/​licenses/​by/​4.​0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.

Published
2014

44. Nanoparticle delivery to the brain - By focused ultrasound and self-assembled nanoparticle-stabilized microbubbles

Author

Åslund, Andreas K. O., Berg, Sigrid, Hak, Sjoerd, Mørch, Yrr, Torp, Sverre H., Sandvig, Axel, Widerøe, Marius, Hansen, Rune, Davies, Catharina de Lange, Åslund, Andreas K. O., Berg, Sigrid, Hak, Sjoerd, Mørch, Yrr, Torp, Sverre H., Sandvig, Axel, Widerøe, Marius, Hansen, Rune, and Davies, Catharina de Lange

Abstract

The blood-brain barrier (BBB) constitutes a significant obstacle for the delivery of drugs into the central nervous system(CNS). Nanoparticles have been able to partly overcome this obstacle and can thus improve drug delivery across the BBB. Furthermore, focused ultrasound in combination with gas filled microbubbles has opened the BBB in a temporospatial manner in animal models, thus facilitating drug delivery across the BBB. In the current study we combine these two approaches in our quest to develop a novel, generic method for drug delivery across the BBB and into the CNS. Nanoparticles were synthesized using the polymer poly(butyl cyanoacrylate) (PBCA), and such nanoparticles have been reported to cross the BBB to some extent. Together with proteins, these nanoparticles self-assemble into microbubbles. Using these novel microbubbles in combination with focused ultrasound, we successfully and safely opened the BBB transiently in healthy rats. Furthermore, we also demonstrated that the nanoparticles could cross the BBB and deliver a model drug into the CNS.

Published
2015
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45. Comparison of Compressive Stress-Relaxation Behavior in Osteoarthritic (ICRS Graded) Human Articular Cartilage.

Author

Kumar, Rajesh, Pierce, David M., Isaksen, Vidar, Davies, Catharina de Lange, Drogset, Jon O., and Lilledahl, Magnus B.

Subjects
OSTEOARTHRITIS, ARTICULAR cartilage diseases, PROTEOGLYCANS, DIAGNOSTIC imaging, TOTAL knee replacement
Abstract

Osteoarthritis (OA) is a common joint disorder found mostly in elderly people. The role of mechanical behavior in the progression of OA is complex and remains unclear. The stress-relaxation behavior of human articular cartilage in clinically defined osteoarthritic stages may have importance in diagnosis and prognosis of OA. In this study we investigated differences in the biomechanical responses among human cartilage of ICRS grades I, II and III using polymer dynamics theory. We collected 24 explants of human articular cartilage (eight each of ICRS grade I, II and III) and acquired stress-relaxation data applying a continuous load on the articular surface of each cartilage explant for 1180 s. We observed a significant decrease in Young’s modulus, stress-relaxation time, and stretching exponent in advanced stages of OA (ICRS grade III). The stretch exponential model speculated that significant loss in hyaluronic acid polymer might be the reason for the loss of proteoglycan in advanced OA. This work encourages further biomechanical modelling of osteoarthritic cartilage utilizing these data as input parameters to enhance the fidelity of computational models aimed at revealing how mechanical behaviors play a role in pathogenesis of OA. [ABSTRACT FROM AUTHOR]

Published
2018
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46. Structural analysis of articular cartilage using multiphoton microscopy : Input for biomechanical modeling

Author

Lilledahl, Magnus B., Pierce, David M., Ricken, Tim, Holzapfel, Gerhard A., Davies, Catharina De Lange, and de Lange Davies, C.

Subjects
Cartilage, Articular, Compressive Strength, Poromechanics, Finite Element Analysis, Models, Biological, Viscoelasticity, Optics, Imaging, Three-Dimensional, Microscopy, medicine, Animals, Computer Simulation, Electrical and Electronic Engineering, Darcy, Bauwissenschaften, Radiological and Ultrasound Technology, business.industry, Cartilage, Finite element method, Elasticity, Computer Science Applications, Extracellular Matrix, medicine.anatomical_structure, Microscopy, Fluorescence, Multiphoton, Finite strain theory, Volume fraction, Collagen, business, Chickens, Software, Biomedical engineering
Abstract

The 3-D morphology of chicken articular cartilage was quantified using multiphoton microscopy (MPM) for use in continuum-mechanical modeling. To motivate this morphological study we propose aspects of a new, 3-D finite strain constitutive model for articular cartilage focusing on the essential load-bearing morphology: an inhomogeneous, poro-(visco)elastic solid matrix reinforced by an anisotropic, (visco)elastic dispersed fiber fabric which is saturated by an incompressible fluid residing in strain-dependent pores. Samples of fresh chicken cartilage were sectioned in three orthogonal planes and imaged using MPM, specifically imaging the collagen fibers using second harmonic generation. Employing image analysis techniques based on Fourier analysis, we derived the principal directionality and dispersion of the collagen fiber fabric in the superficial layer. In the middle layer, objective thresholding techniques were used to extract the volume fraction occupied by extracellular collagen matrix. In conjunction with information available in the literature, or additional experimental testing, we show how this data can be used to derive a 3-D map of the initial solid volume fraction and Darcy permeability.

Published
2011

48. Near-Infrared Fluorescence Energy Transfer Imaging of Nanoparticle Accumulation and Dissociation Kinetics in Tumor-Bearing Mice

Author

Zhao, Yiming, primary, van Rooy, Inge, additional, Hak, Sjoerd, additional, Fay, Francois, additional, Tang, Jun, additional, Davies, Catharina de Lange, additional, Skobe, Mihaela, additional, Fisher, Edward Allen, additional, Radu, Aurelian, additional, Fayad, Zahi. A., additional, de Mello Donegá, Celso, additional, Meijerink, Andries, additional, and Mulder, Willem J. M., additional

Published
2013
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