Gd-nanoparticles functionalization with specific peptides for ß-amyloid plaques targeting

Amyloidoses are characterized by the extracellular deposition of insoluble fibrillar proteinaceous aggregates highly organized into cross-β structure and referred to as amyloid fibrils. Nowadays, the diagnosis of these diseases remains tedious and involves multiple examinations while an early and accurate protein typing is crucial for the patients' treatment. Routinely used neuroimaging techniques such as magnetic resonance imaging (MRI) and positron emission tomography (PET) using Pittsburgh compound B, [11C]PIB, provide structural information and allow to assess the amyloid burden, respectively, but cannot discriminate between different amyloid deposits. Therefore, the availability of efficient multimodal imaging nanoparticles targeting specific amyloid fibrils would provide a minimally-invasive imaging tool useful for amyloidoses typing and early diagnosis. In the present study, we have functionalized gadolinium-based MRI nanoparticles (AGuIX) with peptides highly specific for Aβ amyloid fibrils, LPFFD and KLVFF. The capacity of such nanoparticles grafted with peptide to discriminate among different amyloid proteins, was tested with Aβ(1–42) fibrils and with mutated-(V30M) transthyretin (TTR) fibrils

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Additional file 1: Figure S1. Characterization of functionalized nanoparticles. Figure S2. Zeta potential versus pH of AGuIX (black) and AGuIX@PEG (red). Figure S3. Reaction scheme for the synthesis of AGuIX@PEG@[email protected]. Figure S4. Chromatograms obtained with at UV-Visible absorption at λ =295 nm of the AGuIX@PEG, AGuIX@PEG@LPFFD and AGuIX@PEG@KLVFF . Elementary Analyses of grafted nanoparticles: Table S1. Molar ratio deduced from experimental weight percentage; Table S2. Elementary analyses given in weight percent of element in the compound; Table S3. Comparison of the primary amine content evaluated by elementary analysis and TNBS assays. These results allow assessing the molecular formula obtained by elementary analysis. Figure S5. Standard curves of amine quantification in APTES/TEOS equimolar mixture by TNBS assays. Figure S6. The cyanine 5.5 presents characteristic absorption and emission wavelength λexc max Cy5.5 = 675 nm and λem max Cy5.5 = 692 nm. Table S4. The yield of the grafting was calculated thanks to the comparison of the cyanine fluorescence and the DOTA(Gd3+) chelate before and after removal of the ungrafted dye by tangential purification. Figure S7. Effect of nanoparticles on cell viability. Figure S8. PIB derivative synthesis details. Figure S9. Control of the non-binding of Cy5.5 dye to amyloid plaque in brain section of AD mouse model