Biology subjects

McDannold, N.

Publications and source records attributed to McDannold, N..

3 recordsLinked to original sources

bioRxiv2024

Spatial Profiling of Metals through Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging

The spatial-omic analysis of biomolecules such as nucleic acids, lipids, metabolites, and proteins is advancing the study of biological systems and processes in a physio-pathological context. Here, we describe an innovative matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI MSI) method to detect metals within biological tissues using instrumentation that is widely available in research and clinical laboratories. We characterize the spatial distribution of metals in diverse settings including mouse embryogenesis, genetic disorders leading to abnormal metal accumulation, and preclinical testing for improved platinum-based chemotherapy delivery through focused ultrasound across the blood-brain barrier. Spatial metal profiling will advance research studies and the clinical analysis of metal-related diseases, enabling more precise use of metal-based therapies and advances in diverse scientific fields beyond biomedicine. One-Sentence SummarySpatial metallomic profiling maps native metals or those coordinated to xenobiotics, antibodies, and biomolecules in tissues.

cancer biology↗

bioRxiv2023

Non-invasive homogeneous targeted blood-brain barrier disruption using acoustic holography with a clinical focused ultrasound system

Holographic methods can be used with phased array transducers to shape an ultrasound field. We tested a simple method to create holograms with a 1024-element phased array transducer. With this method, individual acoustic simulations for each element of the transducer were simultaneously loaded into computer memory. Each elements phase was systematically modulated until the combined field matched a desired pattern. The method was evaluated with a 220 kHz hemispherical transducer being tested clinically to enhance drug delivery via blood-brain barrier disruption. The holograms were evaluated in a tissue-mimicking phantom and in vivo in experiments disrupting the blood-brain barrier in rats and in a macaque. This approach can enlarge the focal volume in a patient-specific manner and could reduce the number of sonication targets needed to disrupt large volumes, improve the homogeneity of the disruption, and improve our ability to detect microbubble activity in tissues with low vascular density. TeaserHolography can shape the focal region of a clinical focused ultrasound system developed for targeted drug delivery in the brain.

biophysics↗

bioRxiv2021

Ultrasound-mediated blood-brain barrier disruption improves anti-pyroglutamate3 Aβ antibody efficacy and enhances phagocyte infiltration into brain in aged Alzheimer's disease-like mice

Pyroglutamate-3 amyloid-{beta} (pGlu3 A{beta}) is an N-terminally modified, toxic form of amyloid-{beta} that is present in cerebral amyloid plaques and vascular deposits. Using the Fc-competent murine anti-pGlu3 A{beta} monoclonal antibody (mAb), 07/2a, we present here a nonpharmacological approach using focused ultrasound (FUS) with intravenous (i.v.) injection of microbubbles (MB) to facilitate i.v. delivery of the 07/2a mAb across the blood brain barrier (BBB) in order to improve A{beta} removal and restore memory in aged APP/PS1 mice, an Alzheimers disease (AD)-like model of amyloidogenesis. Compared to sham-treated controls, aged APP/PS1 mice treated with 07/2a immediately prior to FUS-mediated BBB disruption (mAb + FUS-BBBD combination treatment) showed significantly better spatial learning and memory in the Water T Maze. FUS-BBBD treatment alone improved contextual fear learning and memory in aged WT and APP/PS1 mice, respectively. APP/PS1 mice given the combination treatment had reduced A{beta}42 and pGlu3 A{beta} hippocampal plaque burden compared to PBS-treated APP/PS1 mice. Hippocampal synaptic puncta density and synaptosomal synaptic protein levels were also higher in APP/PS1 mice treated with 07/2a just prior to BBB disruption. Increased Iba-1+ microglia were observed in the hippocampi of AD mice treated with 07/2a with and without FUS-BBBD, and APP/PS1 mice that received hippocampal BBB disruption and 07/2a showed increased Ly6G+ monocytes in hippocampal CA3. FUS-induced BBB disruption did not increase the incidence of microhemorrhage in mice with or without 07/2a mAb treatment. Our findings suggest that FUS is useful tool that may enhance delivery of an anti-pGlu3 A{beta} mAb for immunotherapy. FUS-mediated BBB disruption in combination with the 07/2a mAb also appears to facilitate monocyte infiltration in this AD model. Overall, these effects resulted in greater sparing of synapses and improved cognitive function without causing overt damage, suggesting the possibility of FUS as a noninvasive method to increase the therapeutic efficacy in AD patients.

bioengineering↗