On the selection and design of proteins and peptide derivatives for the production of photoluminescent, red-emitting gold quantum clusters

Novel pathways of the synthesis of photoluminescent gold quantum clusters (AuQCs) using biomolecules as reactants provide biocompatible products for biological imaging techniques. In order to rationalize the rules for the preparation of red-emitting AuQCs in aqueous phase using proteins or peptides, the role of different organic structural units was investigated. Three systems were studied: proteins, peptides, and amino acid mixtures, respectively. We have found that cysteine and tyrosine are indispensable residues. The SH/S-S ratio in a single molecule is not a critical factor in the synthesis, but on the other hand, the stoichiometry of cysteine residues and the gold precursor is crucial. These observations indicate the importance of proper chemical behavior of all species in a wide size range extending from the atomic distances (in the AuI-S semi ring) to nanometer distances covering the larger sizes of proteins assuring the hierarchical structure of the whole self-assembled system

Zwitterion functionalized gold nanoclusters for multimodal near infrared fluorescence and photoacoustic imaging

Gold nanoclusters (Au NCs) are an emerging type of theranostic agents combining therapeutic and imaging features with reduced toxicity. Au NCs stabilized by a zwitterion ligand with a fine control of the metal core size and the ligand coverage were synthesized by wet chemistry. Intense fluorescence signal is reported for the highest ligand coverage, whereas photoacoustic signal is stronger for the largest metal core. The best Au NC candidate with an average molecular weight of 17 kDa could be detected with high sensitivity on a 2D-near-infrared imaging instrument (limit of detection (LOD) = 2.3 μM μM ) and by photoacoustic imaging. In vitro and in vivo experiments demonstrate an efficient cell uptake in U87 cell lines, a fast renal clearance (t 1/2α t1/2α = 6.5 ± 1.3 min), and a good correlation between near infrared fluorescence and photoacoustic measurements to follow the early uptake of Au NCs in liver

Combining metal nanoparticles and nanobodies to boost the biomedical imaging in neurodegenerative diseases

Introduction: In the study of neurodegenerative diseases, the possibility to follow the fate of specific cells or molecules within the whole body would be a milestone to better understand the complex evolution of disease mechanisms and to monitor the effects of therapies. The techniques available today do not allow the visualization of disease-relevant cells within the whole tridimensional biological context at high spatial resolution.Methods: Here we show the results from the first validation steps of a novel approach: by combining the conjugate nanobodies anti-glial fibrillary acidic protein (GFAP) and metal-nanoparticles (i.e. 2 nm gold NP) with X-ray phase contrast tomography (XPCT) we would be able to obtain a tridimensional visualization and identification of cells of interest together with the surrounding tissue and the vascular and neuronal networks.Results: By exploiting the X-ray attenuation properties of metal nanoparticles and the specific targeting capabilities of nanobodies, we could give XPCT the specificity it presently lacks, making it no longer a pure morphological but a molecular and targeted imaging technique. In our case, we synthesized and characterized Gold-NP/GFAP nanobody to target the astrocytes of mouse brain.Discussion: The results of the first tests presented in this paper have provided us with information on the feasibility of the approach, encouraging us to carry out further experiments in order to achieve the ultimate goal of setting up this new imaging technique

Combining metal nanoparticles and nanobodies to boost the biomedical imaging in neurodegenerative diseases

Introduction: In the study of neurodegenerative diseases, the possibility to follow the fate of specific cells or molecules within the whole body would be a milestone to better understand the complex evolution of disease mechanisms and to monitor the effects of therapies. The techniques available today do not allow the visualization of disease-relevant cells within the whole tridimensional biological context at high spatial resolution. Methods: Here we show the results from the first validation steps of a novel approach: by combining the conjugate nanobodies anti-glial fibrillary acidic protein (GFAP) and metal-nanoparticles (i.e. 2 nm gold NP) with X-ray phase contrast tomography (XPCT) we would be able to obtain a tridimensional visualization and identification of cells of interest together with the surrounding tissue and the vascular and neuronal networks. Results: By exploiting the X-ray attenuation properties of metal nanoparticles and the specific targeting capabilities of nanobodies, we could give XPCT the specificity it presently lacks, making it no longer a pure morphological but a molecular and targeted imaging technique. In our case, we synthesized and characterized Gold-NP/GFAP nanobody to target the astrocytes of mouse brain. Discussion: The results of the first tests presented in this paper have provided us with information on the feasibility of the approach, encouraging us to carry out further experiments in order to achieve the ultimate goal of setting up this new imaging technique

463P Impact of two waves of Sars-Cov-2 outbreak on the clinical presentation and outcomes of newly referred breast cancer cases at AP-HP: A retrospective multicenter cohort study

International audienceBackgroundThe Sars Cov-2 pandemic and the national lockdowns disrupted healthcare systems in 2020. We assessed the impact on care pathways and clinical outcomes for new breast cancers (BCs) in Paris area.MethodsWe performed a retrospective multicenter cohort study on the data warehouse of Greater Paris University Hospitals (APHP). We identified pts newly referred with BC between Jan 2019, and Dec 2020. We assessed the delays of care management, the initial tumor stage from pathology and baseline PET/CT and CT-scan reports, and the trt categories: breast surgery, exclusive systemic therapy, exclusive radiation therapy, or exclusive best supportive care (BSC). We calculated pts’ 1-year overall survival (OS) and compared indicators for 2019 and 2020.ResultsIn 2019 and 2020, 2,303 and 2,258 patients were newly referred with a BC diag among whom 2,055 and 1,988 female patients underwent a BC treatment, respectively. During the 1st and the 2nd lockdowns, the number of BC diag varied by -18% and by +23% compared to the same periods of 2019. Between 2019 and 2020, the rate of de novo metastatic disease (respectively 15% and 15%, p=0.95) did not differ, neither did the pTNM and the ypTNM distributions (p=0.37 and p=0.31). The time from 1st multidisciplinary meeting to trt did not differ (p=0.23). Pts’ access to reconstructive surgery (15% and 17%, p=0.08) and distribution across trt categories did not vary: tumor resection (73% and 72%), exclusive systemic trt (13% and 14%), exclusive radiation trt (9% and 9%), and exclusive BSC (5% and 5%) (p=0.8), respectively. Age-based subgroup analyses yielded to similar results (p=0,95). The rate of neoadjuvant trt for resected pts was lower in 2019 (16%) compared to 2020 (20%) (p=0.02), especially in patients aged < 50 years (15% vs 21%, p=0,01), respectively. The 1-year OS rates in 2019 vs. 2020 were 99.3% vs. 98.9% (HR=0.96; 95% CI, 0.77-1.2), 72.6% vs. 76.6% (HR=1.28; 95% CI, 0.95-1.72), 96.6% vs. 97.8% (HR=1.09; 95% CI, 0.61-1.94), and 15.5% vs. 15.1% (HR=0.99; 95% CI, 0.72-1.37), in the trt groups, respectively.ConclusionsDespite an initial decrease in new BCs, we did not observe any tumor stage shift, and OS did not vary significantly during Sars-Cov-2

DataSheet1_Combining metal nanoparticles and nanobodies to boost the biomedical imaging in neurodegenerative diseases.docx

Introduction: In the study of neurodegenerative diseases, the possibility to follow the fate of specific cells or molecules within the whole body would be a milestone to better understand the complex evolution of disease mechanisms and to monitor the effects of therapies. The techniques available today do not allow the visualization of disease-relevant cells within the whole tridimensional biological context at high spatial resolution.Methods: Here we show the results from the first validation steps of a novel approach: by combining the conjugate nanobodies anti-glial fibrillary acidic protein (GFAP) and metal-nanoparticles (i.e. 2 nm gold NP) with X-ray phase contrast tomography (XPCT) we would be able to obtain a tridimensional visualization and identification of cells of interest together with the surrounding tissue and the vascular and neuronal networks.Results: By exploiting the X-ray attenuation properties of metal nanoparticles and the specific targeting capabilities of nanobodies, we could give XPCT the specificity it presently lacks, making it no longer a pure morphological but a molecular and targeted imaging technique. In our case, we synthesized and characterized Gold-NP/GFAP nanobody to target the astrocytes of mouse brain.Discussion: The results of the first tests presented in this paper have provided us with information on the feasibility of the approach, encouraging us to carry out further experiments in order to achieve the ultimate goal of setting up this new imaging technique.</p