Purpose: Magnetic spectroscopy of Brownian motion (MSB) has been used previously to measure temperature, viscosity, and cellular binding in vitro. The MSB signal - a ratio of the 5th to 3rd harmonic of the response from magnetic nanoparticles to an oscillating field - provides insight into particle microenvironment. These biosensing capabilities would be productive in vivo but until now were prevented by sensitivity limits. Our goal was to design and create a similar apparatus for work in vivo. In vivo spectroscopy is a viable precursor to imaging, and is essential for drug delivery or therapeutic methods like hyperthermia.
Methods: Coil geometries were modeled to optimize a uniform Helmholtz drive coil and imaging coil with maximal spatial resolution. The completed apparatus includes balancing and trim coils to zero out unwanted background fields. The coils were characterized and experiments were performed to verify consistency with previous in vitro experiments. Finally, as an in vivo experiment, we took MSB spectra on living mice with five week old melanomas injected with 200ug of 100nm starch coated nanoparticles.
Results: The drive coil is capable of sustaining 12.5mT fields up to 1.5kHz with a field variation of 3% throughout the sample volume. The pickup coil is frequency independent and has a vertical and horizontal range of 5mm and 10mm respectively before the MSB signal drops below 50%. The minimum sensitivity is 50-70μg of iron. MSB signal response to viscosity changes shows the same signatures as the in vitro apparatus. The in vivo data showed successful sensing of nanoparticles. We also saw the MSB signal decay with time showing the apparatus can detect changes in particle behavior due to interactions with biology.
Conclusions: We achieved in vivo MSB and due to sufficient sensitivity we are motivated to further work in monitoring in vivo cellular uptake and viscosity.
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http://dx.doi.org/10.1118/1.4734798 | DOI Listing |
Exp Cell Res
January 2025
Department of Biosciences and Biomedical Engineering (BSBE), Indian Institute of Technology Indore (IITI), Indore, India. Electronic address:
Cancer is characterized by unregulated cell proliferation, enabling it to invade and spread to different organs and tissues in the body. Cancer progression is intricately influenced by the complex dynamics within the tumor microenvironment (TME). The TME is a composite and dynamic network comprising cancer cells and various immune cells, including tumor-associated macrophages.
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January 2025
Department of Biosciences and Biomedical Engineering (BSBE), Indian Institute of Technology Indore (IITI), Indore, India. Electronic address:
Dorzolamide (DZD), a Carbonic anhydrase (CA) inhibitor clinically used to lower intraocular pressure, exhibits anti-inflammatory effects owing to the drug's ability to inhibit the TIR domain-containing adaptor protein (TIRAP)-mediated signalling in macrophages. Here, we investigated whether DZD intermediates also demonstrate any anti-inflammatory property like DZD but with a reduced inhibition of CA. We found that several intermediates of DZD show increased binding to TIRAP at the common interface of kinases, such as Protein kinase C-delta (PKCδ) and Bruton's tyrosine kinase (BTK).
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November 2024
Brain and Mental Health Program, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
medRxiv
August 2024
Brain & Mental Health Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.
Pathogens
July 2024
Institute for Clinical and Molecular Virology, Friedrich-Alexander University of Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.
Human cytomegalovirus (HCMV) represents a highly medically important pathogen which has constantly been the subject of both molecular and clinical investigations. HCMV infections, especially those in high-risk patients, still raise many unanswered questions, so current investigations are focused on viral pathogenesis, vaccine development, and options for antiviral drug targeting. To this end, the use of suitable viral strains as well as recombinant reporter constructs in cultured cells and model systems has specific significance.
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