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Article: Maleimide-Thiol Linkages Alter the Biodistribution of SN38 Therapeutic Microbubbles Compared to Biotin-Avidin While Preserving Parity in Tumoral Drug Delivery.

Ingram, Nicola / Abou-Saleh, Radwa H / Race, Amanda D / Loadman, Paul M / Bushby, Richard J / Evans, Stephen D / Coletta, P Louise

Pharmaceutics

2024 Volume 16, Issue 3

Abstract: Therapeutic microbubbles (thMBs) contain drug-filled liposomes linked to microbubbles and targeted to vascular proteins. Upon the application of a destructive ultrasound trigger, drug uptake to tumour is improved. However, the structure of thMBs ... ...

Abstract	Therapeutic microbubbles (thMBs) contain drug-filled liposomes linked to microbubbles and targeted to vascular proteins. Upon the application of a destructive ultrasound trigger, drug uptake to tumour is improved. However, the structure of thMBs currently uses powerful non-covalent bonding of biotin with avidin-based proteins to link both the liposome to the microbubble (MB) and to bind the targeting antibody to the liposome-MB complex. This linkage is not currently FDA-approved, and therefore, an alternative, maleimide-thiol linkage, that is currently used in antibody-drug conjugates was examined. In a systematic manner, vascular endothelial growth factor receptor 2 (VEGFR2)-targeted MBs and thMBs using both types of linkages were examined for their ability to specifically bind to VEGFR2 in vitro and for their ultrasound imaging properties in vivo. Both showed equivalence in the production of the thMB structure, in vitro specificity of binding and safety profiles. In vivo imaging showed subtle differences for thMBs where biotin thMBs had a faster wash-in rate than thiol thMBs, but thiol thMBs were longer-lived. The drug delivery to tumours was also equivalent, but interestingly, thiol thMBs altered the biodistribution of delivery away from the lungs and towards the liver compared to biotin thMBs, which is an improvement in biosafety.
Language	English
Publishing date	2024-03-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics16030434
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Magnetic fields in the solar photosphere.

Bushby, Paul J

Philosophical transactions. Series A, Mathematical, physical, and engineering sciences

2008 Volume 366, Issue 1884, Page(s) 4465–4476

Abstract: Recent high-resolution observations of the surface of the Sun have revealed the fine structure of a vast array of complex photospheric magnetic features. Observations of these magnetic field structures have already greatly enhanced our theoretical ... ...

Abstract	Recent high-resolution observations of the surface of the Sun have revealed the fine structure of a vast array of complex photospheric magnetic features. Observations of these magnetic field structures have already greatly enhanced our theoretical understanding of the interactions between magnetic fields and turbulent convection, and future photospheric observations will inevitably present new theoretical challenges. In this review, I discuss recent progress that has been made in the modelling of photospheric magnetic fields. In particular, I focus upon the complex field structures that are observed within the umbrae and the penumbrae of sunspots. On a much smaller scale, I also discuss models of the highly localized magnetic field structures that are observed in less magnetically active regions of the photosphere. As the spatial resolution of telescopes has improved over the last few years, it has now become possible to observe these features in detail, and theoretical models can now describe much of this behaviour. In the last section of this review, I discuss some of the remaining unanswered questions.
MeSH term(s)	Humans ; Magnetic Fields ; Magnetics ; Models, Theoretical ; Solar Activity ; Solar System
Language	English
Publishing date	2008-12-13
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	208381-4
ISSN	1471-2962 ; 1364-503X ; 0080-4614 ; 0264-3820 ; 0264-3952
ISSN (online)	1471-2962
ISSN	1364-503X ; 0080-4614 ; 0264-3820 ; 0264-3952
DOI	10.1098/rsta.2008.0158
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Article ; Online: Localized oscillatory states in magnetoconvection.

Buckley, Matthew C / Bushby, Paul J

Physical review. E, Statistical, nonlinear, and soft matter physics

2013 Volume 87, Issue 2, Page(s) 23019

Abstract: Localized states are found in many pattern forming systems. The aim of this paper is to investigate the occurrence of oscillatory localized states in two-dimensional Boussinesq magnetoconvection. Initially considering an idealized model, in which the ... ...

Abstract	Localized states are found in many pattern forming systems. The aim of this paper is to investigate the occurrence of oscillatory localized states in two-dimensional Boussinesq magnetoconvection. Initially considering an idealized model, in which the vertical structure of the system has been simplified by a projection onto a small number of Fourier modes, we find that these states are restricted to the low ζ regime (where ζ represents the ratio of the magnetic to thermal diffusivities). These states always exhibit bistability with another nontrivial solution branch; in other words, they show no evidence of subcritical behavior. This is due to the weak flux expulsion that is exhibited by these time-dependent solutions. Using the results of this parameter survey, we locate corresponding states in a fully resolved two-dimensional system, although the mode of oscillation is more complex in this case. This is the first time that a localized oscillatory state, of this kind, has been found in a fully resolved magnetoconvection simulation.
MeSH term(s)	Computer Simulation ; Magnetic Fields ; Models, Theoretical ; Oscillometry/methods ; Rheology/methods
Language	English
Publishing date	2013-02
Publishing country	United States
Document type	Journal Article
ISSN	1550-2376
ISSN (online)	1550-2376
DOI	10.1103/PhysRevE.87.023019
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Article ; Online: Targeted microbubbles carrying lipid-oil-nanodroplets for ultrasound-triggered delivery of the hydrophobic drug, combretastatin A4.

Charalambous, Antonia / Mico, Victoria / McVeigh, Laura E / Marston, Gemma / Ingram, Nicola / Volpato, Milène / Peyman, Sally A / McLaughlan, James R / Wierzbicki, Antonia / Loadman, Paul M / Bushby, Richard J / Markham, Alexander F / Evans, Stephen D / Coletta, P Louise

Nanomedicine : nanotechnology, biology, and medicine

2021 Volume 36, Page(s) 102401

Abstract: The hydrophobicity of a drug can be a major challenge in its development and prevents the clinical translation of highly potent anti-cancer agents. We have used a lipid-based nanoemulsion termed Lipid-Oil-Nanodroplets (LONDs) for the encapsulation and in ...

Abstract	The hydrophobicity of a drug can be a major challenge in its development and prevents the clinical translation of highly potent anti-cancer agents. We have used a lipid-based nanoemulsion termed Lipid-Oil-Nanodroplets (LONDs) for the encapsulation and in vivo delivery of the poorly bioavailable combretastatin A4 (CA4). Drug delivery with CA4 LONDs was assessed in a xenograft model of colorectal cancer. LC-MS/MS analysis revealed that CA4 LONDs, administered at a drug dose four times lower than drug control, achieved equivalent concentrations of CA4 intratumorally. We then attached CA4 LONDs to microbubbles (MBs) and targeted this construct to VEGFR2. A reduction in tumor perfusion was observed in CA4 LONDs-MBs treated tumors. A combination study with irinotecan demonstrated a greater reduction in tumor growth and perfusion (P = 0.01) compared to irinotecan alone. This study suggests that LONDs, either alone or attached to targeted MBs, have the potential to significantly enhance tumor-specific hydrophobic drug delivery.
MeSH term(s)	Animals ; Cell Line, Tumor ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/metabolism ; Colorectal Neoplasms/pathology ; Humans ; Hydrophobic and Hydrophilic Interactions ; Lipids/chemistry ; Lipids/pharmacokinetics ; Lipids/pharmacology ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Microbubbles ; Nanostructures/chemistry ; Nanostructures/therapeutic use ; Stilbenes/chemistry ; Stilbenes/pharmacokinetics ; Stilbenes/pharmacology ; Ultrasonography ; Xenograft Model Antitumor Assays
Chemical Substances	Lipids ; Stilbenes ; fosbretabulin (I5590ES2QZ)
Language	English
Publishing date	2021-04-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2183417-9
ISSN	1549-9642 ; 1549-9634
ISSN (online)	1549-9642
ISSN	1549-9634
DOI	10.1016/j.nano.2021.102401
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Article: Elastin-Like Protein, with Statherin Derived Peptide, Controls Fluorapatite Formation and Morphology.

Shuturminska, Kseniya / Tarakina, Nadezda V / Azevedo, Helena S / Bushby, Andrew J / Mata, Alvaro / Anderson, Paul / Al-Jawad, Maisoon

Frontiers in physiology

2017 Volume 8, Page(s) 368

Abstract: The process of enamel biomineralization is multi-step, complex and mediated by organic molecules. The lack of cells in mature enamel leaves it unable to regenerate and hence novel ways of growing enamel-like structures are currently being investigated. ... ...

Abstract	The process of enamel biomineralization is multi-step, complex and mediated by organic molecules. The lack of cells in mature enamel leaves it unable to regenerate and hence novel ways of growing enamel-like structures are currently being investigated. Recently, elastin-like protein (ELP) with the analog
Language	English
Publishing date	2017-06-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2017.00368
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Book ; Online: On Predicting the Solar Cycle using Mean-Field Models

Bushby, Paul J. / Tobias, Steven M.

2007

Abstract: We discuss the difficulties of predicting the solar cycle using mean-field models. Here we argue that these difficulties arise owing to the significant modulation of the solar activity cycle, and that this modulation arises owing to either stochastic or ... ...

Abstract	We discuss the difficulties of predicting the solar cycle using mean-field models. Here we argue that these difficulties arise owing to the significant modulation of the solar activity cycle, and that this modulation arises owing to either stochastic or deterministic processes. We analyse the implications for predictability in both of these situations by considering two separate solar dynamo models. The first model represents a stochastically-perturbed flux transport dynamo. Here even very weak stochastic perturbations can give rise to significant modulation in the activity cycle. This modulation leads to a loss of predictability. In the second model, we neglect stochastic effects and assume that generation of magnetic field in the Sun can be described by a fully deterministic nonlinear mean-field model -- this is a best case scenario for prediction. We designate the output from this deterministic model (with parameters chosen to produce chaotically modulated cycles) as a target timeseries that subsequent deterministic mean-field models are required to predict. Long-term prediction is impossible even if a model that is correct in all details is utilised in the prediction. Furthermore, we show that even short-term prediction is impossible if there is a small discrepancy in the input parameters from the fiducial model. This is the case even if the predicting model has been tuned to reproduce the output of previous cycles. Given the inherent uncertainties in determining the transport coefficients and nonlinear responses for mean-field models, we argue that this makes predicting the solar cycle using the output from such models impossible. Comment: 22 Pages, 5 Figures, Preprint accepted for publication in ApJ
Keywords	Astrophysics
Subject code	621
Publishing date	2007-04-18
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Ultrasound-triggered therapeutic microbubbles enhance the efficacy of cytotoxic drugs by increasing circulation and tumor drug accumulation and limiting bioavailability and toxicity in normal tissues.

Ingram, Nicola / McVeigh, Laura E / Abou-Saleh, Radwa H / Maynard, Juliana / Peyman, Sally A / McLaughlan, James R / Fairclough, Michael / Marston, Gemma / Valleley, Elizabeth M A / Jimenez-Macias, Jorge L / Charalambous, Antonia / Townley, William / Haddrick, Malcolm / Wierzbicki, Antonia / Wright, Alexander / Volpato, Milène / Simpson, Peter B / Treanor, Darren E / Thomson, Neil H /

Loadman, Paul M / Bushby, Richard J / Johnson, Benjamin R G / Jones, Pamela F / Evans, J Anthony / Freear, Steven / Markham, Alexander F / Evans, Stephen D / Coletta, P Louise

Theranostics

2020 Volume 10, Issue 24, Page(s) 10973–10992

Abstract: Most cancer patients receive chemotherapy at some stage of their treatment which makes improving the efficacy of cytotoxic drugs an ongoing and important goal. Despite large numbers of potent anti-cancer agents being developed, a major obstacle to ... ...

Abstract	Most cancer patients receive chemotherapy at some stage of their treatment which makes improving the efficacy of cytotoxic drugs an ongoing and important goal. Despite large numbers of potent anti-cancer agents being developed, a major obstacle to clinical translation remains the inability to deliver therapeutic doses to a tumor without causing intolerable side effects. To address this problem, there has been intense interest in nanoformulations and targeted delivery to improve cancer outcomes. The aim of this work was to demonstrate how vascular endothelial growth factor receptor 2 (VEGFR2)-targeted, ultrasound-triggered delivery with therapeutic microbubbles (thMBs) could improve the therapeutic range of cytotoxic drugs.
MeSH term(s)	Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/pharmacokinetics ; Biological Availability ; Cell Line, Tumor ; Colorectal Neoplasms/diagnostic imaging ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/pathology ; Combined Modality Therapy/methods ; Drug Delivery Systems/methods ; Female ; Humans ; Irinotecan ; Microbubbles/therapeutic use ; Microfluidic Analytical Techniques ; Positron-Emission Tomography ; Tissue Distribution/radiation effects ; Ultrasonic Waves ; Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors ; Vascular Endothelial Growth Factor Receptor-2/metabolism ; Xenograft Model Antitumor Assays
Chemical Substances	Antineoplastic Agents ; Irinotecan (7673326042) ; KDR protein, human (EC 2.7.10.1) ; Vascular Endothelial Growth Factor Receptor-2 (EC 2.7.10.1)
Language	English
Publishing date	2020-09-01
Publishing country	Australia
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2592097-2
ISSN	1838-7640 ; 1838-7640
ISSN (online)	1838-7640
ISSN	1838-7640
DOI	10.7150/thno.49670
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Article ; Online: Protein disorder-order interplay to guide the growth of hierarchical mineralized structures.

Nature communications

2018 Volume 9, Issue 1, Page(s) 2145

Abstract: A major goal in materials science is to develop bioinspired functional materials based on the precise control of molecular building blocks across length scales. Here we report a protein-mediated mineralization process that takes advantage of disorder- ... ...

Abstract	A major goal in materials science is to develop bioinspired functional materials based on the precise control of molecular building blocks across length scales. Here we report a protein-mediated mineralization process that takes advantage of disorder-order interplay using elastin-like recombinamers to program organic-inorganic interactions into hierarchically ordered mineralized structures. The materials comprise elongated apatite nanocrystals that are aligned and organized into microscopic prisms, which grow together into spherulite-like structures hundreds of micrometers in diameter that come together to fill macroscopic areas. The structures can be grown over large uneven surfaces and native tissues as acid-resistant membranes or coatings with tuneable hierarchy, stiffness, and hardness. Our study represents a potential strategy for complex materials design that may open opportunities for hard tissue repair and provide insights into the role of molecular disorder in human physiology and pathology.
MeSH term(s)	Amino Acid Sequence ; Calcification, Physiologic ; Dental Enamel/chemistry ; Dentin/chemistry ; Dentin/metabolism ; Dentin/ultrastructure ; Elastin/chemistry ; Elastin/metabolism ; Elastin/ultrastructure ; Humans ; Hydroxyapatites/chemistry ; Hydroxyapatites/metabolism ; Intrinsically Disordered Proteins/chemistry ; Intrinsically Disordered Proteins/metabolism ; Microscopy, Atomic Force ; Microscopy, Electron, Scanning ; Microscopy, Electron, Transmission ; Minerals/chemistry ; Minerals/metabolism ; Spectroscopy, Fourier Transform Infrared ; X-Ray Diffraction
Chemical Substances	Hydroxyapatites ; Intrinsically Disordered Proteins ; Minerals ; Elastin (9007-58-3)
Language	English
Publishing date	2018-06-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-018-04319-0
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Article ; Online: Protein disorder–order interplay to guide the growth of hierarchical mineralized structures

Nature Communications, Vol 9, Iss 1, Pp 1-

2018 Volume 12

Abstract: There is evidence that disordered proteins play a role in the mineralization process. Here, the authors report on the development of elastin-like recombinant protein membranes using disordered-ordered interplay to investigate and guide mineralization. ...

Abstract	There is evidence that disordered proteins play a role in the mineralization process. Here, the authors report on the development of elastin-like recombinant protein membranes using disordered-ordered interplay to investigate and guide mineralization.
Keywords	Science ; Q
Language	English
Publishing date	2018-06-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Protein disorder–order interplay to guide the growth of hierarchical mineralized structures

Nature Communications, Vol 9, Iss 1, Pp 1-

2018 Volume 12

Abstract	There is evidence that disordered proteins play a role in the mineralization process. Here, the authors report on the development of elastin-like recombinant protein membranes using disordered-ordered interplay to investigate and guide mineralization.
Keywords	Science ; Q
Language	English
Publishing date	2018-06-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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