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In Vivo and In Vitro Monitoring of Amyloid Aggregation via BSA@FGQDs Multimodal Probe

M. Yousaf, M. Ahmad, I. Bhatti, Abdul Nasir, M. Hasan, Xian Jian, K. Kalantar-zadeh, N. Mahmood

ACS Sensors, 2018

57 citations

Abstract

Early detection of peptide aggregate intermediates is quite challenging because of their variable and complex nature as well as due to lack of reliable sensors for diagnosis. Herein, we report the detection of monomers and oligomers using specified fluorescence and a magnetic resonance imaging (MRI) multimodal probe based on bovine-serum-albumin-capped fluorine functionalized graphene quantum dots (BSA@FGQDs). This probe enables in vitro fluorescence-based monitoring of human islet amyloid polypeptide (hIAPP), insulin, and amyloid β(1-42) (Aβ42) monomers and oligomers during the fibrillogenesis dynamic. Up to 90% fluorescence quenching of BSA@FGQDs probe upon addition of amyloid monomers/oligomers was observed due to static quenching and nonradiative energy transfer. Moreover, the BSA@FGQDs probe shows 10 times higher signals in detecting amyloid intermediates and fibrils than that of conventional thioflavin dye. A negative Δ G° value (-36.21 kJ/mol) indicates spontaneous interaction of probe with the peptide. These interactions are hydrogen bonding and hydrophobic as proved by thermodynamic parameters. Visual binding clues of BSA@FGQDs with different morphological states of amyloid protein was achieved through electron microscopy. Furthermore, intravenous and intracranial injection of BSA@FGQDs probe in Alzheimer model mice brain enabled in vivo detection of amyloid plaques in live mice brain by 19F MRI through contrast enhancement. Our proposed probe not only effectively…

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