| Autor: |
Barooah, Nilotpal, Karmakar, Puja, Sharanya, M. K., Mishra, Monalisa, Bhasikuttan, Achikanath C., Mohanty, Jyotirmayee |
| Zdroj: |
Journal of Materials Chemistry B; 10/21/2023, Vol. 11 Issue 39, p9545-9554, 10p |
| Abstrakt: |
Customised perylenediimide (PDI) chromophores find diverse applications not only as chemosensors, inorganic–organic semiconductors, photovoltaics, photocatalysts, etc., but also in protein surface engineering, bio-sensors and drug delivery systems. This study focuses on the interaction of a custom synthesized phenylalanine derivatized perylenediimide (L -Phe-PDI) dye with a model protein, insulin, and its structurally distinct fibrils to develop fluorescence sensors for fibrillar aggregates and in vivo imaging applications. Detailed photophysical studies revealed that L -Phe-PDI gets aggregated in the presence of insulin and causes emission quenching at pH 7.4, which in the absence of insulin occurs only at pH ∼2. During in vitro incubation of insulin to its fibrils, the fluorescence intensity of the L -Phe-PDI probe is enhanced to ∼150 fold in a two-stage manner, manifesting the pathways of structural transformation to β-sheet rich mature fibrils. The in vivo sensing has further been validated in living models of the Aβ-mutant Drosophila fly, which is known to develop progressive neurodegeneration comparable to that of human brains with Alzheimer's disease (AD). Bioimaging of the L -Phe-PDI treated Aβ-mutant Drosophila documented the blood–brain/blood–retina-barrier cross-over ability of L -Phe-PDI with no toxic effects. Comparison of the fibrillar images from the brain and eye region with the reference thioflavin T (ThT) probe established the uptake of L -Phe-PDI by the aggregate/fibrillar moieties. The samples from L -Phe-PDI-treated flies apparently displayed reduced fibrillar spots, a possible case of L -Phe-PDI-induced disintegration of fibrillar aggregates at large, an observation substantiated by the improved phenotype activities as compared to the untreated flies. The findings reported both in vitro and in vivo with the L -Phe-PDI material for the first time open up avenues to explore the therapeutic potential of custom-designed PDI derivatives for amyloid fibril sensors and bioimaging. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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