Biology subjects

Nash, L.

Publications and source records attributed to Nash, L..

3 recordsLinked to original sources

bioRxiv2026

Modular Albumin-Chaperoned NIR-II Nanofluorophores Enables Pan-Ovarian Cancer Imaging Across Multiscale Tumor Models

Ovarian cancer remains the most lethal gynecological malignancy, primarily due to late-stage diagnosis and the challenges of achieving complete cytoreduction. While fluorescence image-guided surgery (FIGS) offers intraoperative visualization, current clinical agents are limited by insufficient brightness, rapid photobleaching, and poor molecular selectivity, particularly in the near-infrared window. Here, we report the rational modular design of ultrabright NIR-II semiconducting polymer (SP) nanofluorophores for high-fidelity ovarian cancer imaging. By nanoconfining of a representative hydrophobic SP within a functional albumin matrix induces a "chaperone" effect that suppresses aggregation-induced quenching and shifts emission in the NIR-II window (1000-1250 nm). This platform integrates a dual-receptor targeting strategy, leveraging intrinsic albumin-receptor interactions (GP60 and SPARC) alongside folate receptor alpha (FR) functionalization. This synergistic approach enables pan-ovarian cancer imaging by ensuring high-affinity binding across diverse tumor phenotypes, regardless of heterogeneous receptor expression. Across a multiscale validation framework, the nanofluorophores demonstrate efficient receptor-mediated endocytosis in 2D cultures and deep interstitial penetration in 3D tumor spheroids. Furthermore, microfluidic tumor-on-chip models incorporating endothelial-like fenestrations confirm controlled extravasation and targeting under physiological shear stress. 3D bioprinted tumor phantoms and ex vivo porcine ovary tissues further confirm that BSA-FA@SP2 provides superior lesion delineation and signal-to-background ratios compared to indocyanine green, a clinical standard. Importantly, the nanofluorophores exhibit excellent hemocompatibility, with minimal hemolysis and negligible complement activation, indicating a non-immunogenic, stealth profile. Collectively, this work establishes albumin-shielded NIR-II nanofluorophores as a robust platform for precision intraoperative pan-ovarian imaging and advances the translational potential of nanotechnology-enabled surgical oncology.

bioengineering↗

bioRxiv2025

Spinal electrophysiology reveals frequency-specific spatial patterns of neural activity and corticospinal coherence during pincer-grip

BackgroundNeural dynamics within sensory-motor networks involved in motor control exhibit well-established frequency-dependent patterns of cortical activity. In contrast, corresponding neural patterns of spinal cord activity remain poorly understood. As an active functional part of motor control, characterising spinal cord activity is essential for understanding sensorimotor function. High-density electrospinography presents a novel technique to assess spinal neural dynamics by non-invasively recording task-relevant electrical activity. ObjectiveTo non-invasively investigate spatio-spectral patterns of task-related spinal activity and its functional connectivity with cortical regions during isometric pincer-grip contraction. MethodologyHere, we simultaneously recorded 128-channel electroencephalography (EEG), 64-channel electrospinography (ESG), and two bipolar electromyography (EMG) signals during an isometric pincer-grip task. Frequency-specific spatial patterns of spinal activity and cortico-spinal connectivity were evaluated by calculating task-related ESG power and cortico-spinal coherence between ESG and EEG signals during the isometric hold. ResultsDistinct frequency-specific spatial patterns of spinal activity were observed at lower cervical levels during sustained hold, with significant activation over the ipsilateral anterolateral region. In the beta band, task-related spinal activity was significantly ipsilateralised, and exhibited significant cortico-spinal connectivity between contralateral motor cortex and ipsi-anterolateral spinal region. ConclusionsThis first-of-its-kind application of HD non-invasive spinal electrophysiology revealed that the spinal cord exhibits distinct frequency-specific spatial activation and cortical connectivity patterns during pincer-grip sustained hold. Specifically, the ipsi-anterolateral spinal region demonstrated high task-relevance, potentially indicating anterior horn activity and its connectivity with motor cortex. Furthermore, beta-band activation was observed as a key signature during sustained hold, further underpinning its relevance during motor control.

neuroscience↗

bioRxiv2024

SC10X/U: A High-density Electrode System for Non-Invasive Recording of Neural Activity of the Cervical Spinal Cord

ObjectiveTo design and develop a high-density (HD) electrode system that describes the position of surface electrodes for recording electrophysiological signals from the human cervical spinal cord. The system is intended to standardize experimental recordings and facilitate the subsequent analysis of evoked and spontaneous spinal cord neural activity, using high-density electrospinography (HD-ESG). MethodThe proposed system (SC10-X/U) describes the locations of up to 76 channels with a unique nomenclature, where the division of the spinal cord (SC) electrode space was inspired by the EEG 10-10 system. As proof of concept, spinal evoked potentials in response to median nerve stimulation at the wrist were recorded from 10 participants and characterized based on a 64-channel derivation from the SC10-X/U system. ResultsFollowing the design criteria, the SC10-X/U defines 76 electrode positions and its configuration. HD-ESG system was utilized to successfully record evoked spinal responses and significant N13 and P9 potential were observed in response to the stimulation. The spinal N13 potential had a latency of 13.2 +-1.1ms (mean +-SD) after stimulation. A topographic map of the N13 electro-spinal activity using the 64-channel recording system revealed an epicentre at C5-C7 dorsal-vertebral locations (ML4 - ML6 electrodes). ConclusionThe proposed SC10-X/U system will facilitate standardized recording and analysis of high-density ESG signals from the human cervical spinal cord. The system defines electrode locations to promote standardization across different individuals, studies, and clinical and research centres. The HD-ESG evoked potentials recorded using the proposed system were comparable to those observed in previous non-HD studies. The presented topographic maps conform to known neurophysiological and neuroanatomical findings. This served to validate the design and development of the electrode system and patch for future studies.

neuroscience↗