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Author: Nair, Roshna V. Ă— End date: 2024 Ă— Start date: 2020 Ă— DDC: 540 Ă—

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    Light-Regulated Angiogenesis via a Phototriggerable VEGF Peptidomimetic
    (Weinheim : Wiley-VCH, 2021) Nair, Roshna V.; Farrukh, Aleeza; del Campo, Aránzazu
    The application of growth factor based therapies in regenerative medicine is limited by the high cost, fast degradation kinetics, and the multiple functions of these molecules in the cell, which requires regulated delivery to minimize side effects. Here a photoactivatable peptidomimetic of the vascular endothelial growth factor (VEGF) that allows the light-controlled presentation of angiogenic signals to endothelial cells embedded in hydrogel matrices is presented. A photoresponsive analog of the 15-mer peptidomimetic Ac-KLTWQELYQLKYKGI-NH2 (abbreviated PQK) is prepared by introducing a 3-(4,5-dimethoxy-2-nitrophenyl)-2-butyl (DMNPB) photoremovable protecting group at the Trp4 residue. This modification inhibits the angiogenic potential of the peptide temporally. Light exposure of PQK modified hydrogels provide instructive cues to embedded endothelial cells and promote angiogenesis at the illuminated sites of the 3D culture, with the possibility of spatial control. PQK modified photoresponsive biomaterials offer an attractive approach for the dosed delivery and spatial control of pro-angiogenic factors to support regulated vascular growth by just using light as an external trigger.
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    Possibilities and Limitations of Photoactivatable Cytochalasin D for the Spatiotemporal Regulation of Actin Dynamics
    (Washington, D.C. : American Chemical Society, 2020) Nair, Roshna V.; Zhao, Shifang; Terriac, Emmanuel; Lautenschläger, Franziska; Hetmanski, Joseph H.R.; Caswell, Patrick T.; del Campo, Aranzazu
    The study of the actin cytoskeleton and related cellular processes requires tools to specifically interfere with actin dynamics in living cell cultures, ideally with spatiotemporal control and compatible with real time imaging. A phototriggerable derivative of the actin disruptor Cytochalasin D (CytoD) is described and tested here. It includes a nitroveratryloxycarbonyl (Nvoc) photoremovable protecting group (PPG) at the hydroxyl group at C7 of CytoD. The attachment of the PPG renders Nvoc-CytoD temporarily inactive, and enables light-dosed delivery of the active drug CytoD to living cells. This article presents the full structural and physicochemical characterization, the toxicity analysis. It is complemented with biological tests to show the time scales (seconds) and spatial resolution (cellular level) achievable with a UV source in a regular microscopy setup