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

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Abstract
Early detection of peptide aggregates 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 monomers and oligomers specified fluorescence and 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 oligomer during fibrillogenesis dynamic. Up to 90% fluorescence quenching of BSA@FGQDs probe upon addition of amyloid monomers/oligomers was observed due to static quenching and non-radiative energy transfer. Moreover, BSA@FGQDs probe shows 10 times higher signals in detecting amyloid intermediates and fibrils than that of conventional thioflavin dye. Negative ΔG° value (-36.21 kJ/mol) indicates spontaneous interaction of probe with peptide. Theses interaction 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 monitor in-vitro fibrillation kinetics of number of amyloid proteins with higher sensitivity and specificity than thioflavin dye, but also presence of 19F center makes BSA@FGQDs effective probe as a non-invasive and non-radiative in-vivo amyloid plaques detection probe.
Funding Information
  • Peking University
  • University of Agriculture, Faisalabad
  • National Natural Science Foundation of China
  • National Center for Nanoscience and Technology, Chinese Academy of Sciences

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