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

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 ΔG° 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 monitors in vitro fibrillation kinetics of number of amyloid proteins with higher sensitivity and specificity than thioflavin dye, but also, the presence of a 19F center makes BSA@FGQDs an effective probe as a noninvasive and nonradiative in vivo detection probe for amyloid plaques.

Fractionation of Biomolecules in Withania coagulans Extract for Bioreductive Nanoparticle Synthesis, Antifungal and Biofilm Activity

“…The increasing resistance of microbes against antibiotics calls for the urgent discovery of unique biomolecules from extracts of plants like W. coagulans that are of potential interest for their antibiofilm and antifungal activity and as bioreducing agents for the synthesis of cobalt oxide nanoparticles (Co 3 O 4 NPs). The species W. coagulans is highly acclaimed in the Indian ayurvedic system of medicine, where it is known for its medicinal significance in promoting physical and mental health [26,27]. Its active components include alkaloids, steroidal compounds, lactones, withaferin a [28], withanoloids [29], withanone [30], etc.…”

Novel Carbon Dots Derived from Puerariae lobatae Radix and Their Anti-Gout Effects

“…Despite these major achievements, problems such as production costs and environmental toxicity have followed. In order to obtain safe and effective target products, researchers have used various strategies, such as replacing inorganic materials with organic ones in the production process and adopting biosynthesis technology [27,28,29,30]. Impressively, in this paper, biomass was used as the major material, and no metal sites, strong solvents, or strong acids were imported or used during the synthetic process, which indicates that the improved synthetic method used is environmentally friendlier, greener, and safer than previously reported methods.…”

Molecular Imaging of Fluorinated Probes for Tau Protein and Amyloid-β Detection

“…Bovine serum albumin (BSA) was capped onto the FGQDs and was able to bind to amyloid intermediates by π-π stacking interactions and carboxyl/amino groups. The probe was effective in monitoring in vitro amyloid aggregation with a higher specificity and selectivity than thioflavin dye and was suitable for in vivo MRI detection, since it was able to pass the blood-brain barrier and contains 19F ( Figure 2 ) [ 27 ].…”

“… 19F MRI signals of bovine serum albumin@F-functionalized graphene quantum dots (BSA@FGQDs) in normal ( a ) and Alzheimer’s disease (AD) ( b ) mice overlaid on top of a high-resolution T1-weighted proton MRI image [ 27 ]. Arrows indicate the detection of in vivo amyloid plaques.…”

“…Arrows indicate the detection of in vivo amyloid plaques. Images are reprinted with permission from the publisher [ 27 ].…”