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  1. Article: Dynamic molecular exchange and conformational transitions of alpha-synuclein at the nano-bio interface

    Tira, Roberto / De Cecco, Elena / Rigamonti, Valentina / Santambrogio, Carlo / Barracchia, Carlo Giorgio / Munari, Francesca / Romeo, Alessandro / Legname, Giuseppe / Prosperi, Davide / Grandori, Rita / Assfalg, Michael

    International journal of biological macromolecules. 2020 July 01, v. 154

    2020  

    Abstract: The notion that nanoscale surfaces influence protein conformational transitions stimulates the investigation of fibrillogenic polypeptides adsorbing to nanomaterials. Alpha-synuclein (αS) is a prototypical amyloidogenic protein whose aggregation is ... ...

    Abstract The notion that nanoscale surfaces influence protein conformational transitions stimulates the investigation of fibrillogenic polypeptides adsorbing to nanomaterials. Alpha-synuclein (αS) is a prototypical amyloidogenic protein whose aggregation is associated with severe neurodegenerative disorders. We explored the interaction of αS with silica nanoparticles (SNPs) in diverse solution conditions, ranging from protein-free to protein-rich media. We found that the SNP-binding region of αS, determined by site-resolved NMR spectroscopy, was similar in simple buffer and blood serum. Competition binding experiments with isotopic homologues and different proteins showed that cosolutes elicited molecular exchange in a protein-specific manner. The interaction of an oxidized, fibrillation-resistant protein form with SNPs was similar to that of unmodified αS. SNPs, however, did not stimulate fibrillation of the oxidized protein, which remained fibrillation incompetent. CD experiments revealed SNP-induced perturbations of the structural properties of oxidized and non-oxidized αS. Thus, while αS binding to SNPs is essentially orthogonal to fibril formation, the interaction perturbs the distribution of conformational states populated by the protein in the colloidal suspension. This study sheds light on the dynamic nature of αS interactions with NPs, an aspect that crucially impacts on our ability to control aggregation of αS.
    Keywords blood serum ; colloids ; nanoparticles ; neurodegenerative diseases ; nuclear magnetic resonance spectroscopy ; oxidation ; polypeptides ; proteins ; silica ; solutes
    Language English
    Dates of publication 2020-0701
    Size p. 206-216.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 282732-3
    ISSN 1879-0003 ; 0141-8130
    ISSN (online) 1879-0003
    ISSN 0141-8130
    DOI 10.1016/j.ijbiomac.2020.03.118
    Database NAL-Catalogue (AGRICOLA)

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  2. Article ; Online: 99m

    Rainone, Paolo / De Palma, Antonella / Sudati, Francesco / Roffia, Valentina / Rigamonti, Valentina / Salvioni, Lucia / Colombo, Miriam / Ripamonti, Marilena / Spinelli, Antonello Enrico / Mazza, Davide / Mauri, Pierluigi / Moresco, Rosa Maria / Prosperi, Davide / Belloli, Sara

    International journal of nanomedicine

    2021  Volume 16, Page(s) 1943–1960

    Abstract: Introduction: The overexpression of Human Epidermal Growth Factor Receptor 2 (HER2) is usually associated with aggressive and infiltrating breast cancer (BC) phenotype, and metastases. Functionalized silica-based nanocarriers (SiNPs) can be labeled for ... ...

    Abstract Introduction: The overexpression of Human Epidermal Growth Factor Receptor 2 (HER2) is usually associated with aggressive and infiltrating breast cancer (BC) phenotype, and metastases. Functionalized silica-based nanocarriers (SiNPs) can be labeled for in vivo imaging applications and loaded with chemotherapy drugs, making possible the simultaneous noninvasive diagnosis and treatment (theranostic) for HER2-positive BC.
    Methods: Firstly, FITC-filled SiNPs, were engineered with two different amounts of Hc-TZ (trastuzumab half-chain) per single nanoparticle (1:2 and 1:8, SiNPs to Hc-TZ ratio), which was
    Results: SiNPs-TZ (1:8 Hc-TZ) tumor uptake was significantly greater than that of SiNPs-TZ (1:2 Hc-TZ) at 6 hours post-injection (p.i.) in ex vivo biodistribution experiment. At 24 h p.i., radioactivity values remained steady. Fluorescence microscopy, confirmed the presence of radiolabeled SiNPs-TZ (1:8 Hc-TZ) within tumor even at later times. SiNPs-TZ (1:8 Hc-TZ) nanoparticles loaded with Doxorubicin (DOX-SiNPs-TZ) showed a similar DOX delivery capability than Caelyx (at 6 h p.i.), in in vitro and ex vivo assays. Nevertheless, at the end of treatment, tumor volume was significantly reduced by DOX-SiNPs-TZ (1:8 Hc-TZ), compared to Caelyx and DOX-SiNPs treatment. Proteomics study identified 88 high stringent differentially expressed proteins comparing the three treatment groups with controls.
    Conclusion: These findings demonstrated a promising detection specificity and treatment efficacy for our system (SiNPs-TZ, 1:8 Hc-TZ), encouraging its potential use as a new theranostic agent for HER2-positive BC lesions. In addition, proteomic profile confirmed that a set of proteins, related to tumor aggressiveness, were positively affected by targeted nanoparticles.
    MeSH term(s) Animals ; Breast Neoplasms/diagnosis ; Breast Neoplasms/diagnostic imaging ; Breast Neoplasms/drug therapy ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Disease Models, Animal ; Doxorubicin/analogs & derivatives ; Doxorubicin/chemistry ; Doxorubicin/pharmacology ; Doxorubicin/therapeutic use ; Drug Carriers/chemistry ; Endocytosis ; Female ; Fluorescein-5-isothiocyanate/chemistry ; Humans ; Mice, Inbred BALB C ; Mice, Nude ; Nanoparticles/chemistry ; Polyethylene Glycols/chemistry ; Polyethylene Glycols/pharmacology ; Polyethylene Glycols/therapeutic use ; Proteome/metabolism ; Proteomics ; Radiopharmaceuticals/chemistry ; Radiopharmaceuticals/pharmacokinetics ; Receptor, ErbB-2/metabolism ; Silicon Dioxide/chemistry ; Technetium/chemistry ; Technetium/pharmacokinetics ; Tissue Distribution/drug effects ; Tomography, Emission-Computed, Single-Photon ; Treatment Outcome ; Mice
    Chemical Substances Drug Carriers ; Proteome ; Radiopharmaceuticals ; liposomal doxorubicin ; Polyethylene Glycols (3WJQ0SDW1A) ; Technetium (7440-26-8) ; Silicon Dioxide (7631-86-9) ; Doxorubicin (80168379AG) ; ERBB2 protein, human (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1) ; Fluorescein-5-isothiocyanate (I223NX31W9)
    Language English
    Publishing date 2021-03-08
    Publishing country New Zealand
    Document type Journal Article
    ZDB-ID 2364941-0
    ISSN 1178-2013 ; 1176-9114
    ISSN (online) 1178-2013
    ISSN 1176-9114
    DOI 10.2147/IJN.S276033
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Dynamic molecular exchange and conformational transitions of alpha-synuclein at the nano-bio interface.

    Tira, Roberto / De Cecco, Elena / Rigamonti, Valentina / Santambrogio, Carlo / Barracchia, Carlo Giorgio / Munari, Francesca / Romeo, Alessandro / Legname, Giuseppe / Prosperi, Davide / Grandori, Rita / Assfalg, Michael

    International journal of biological macromolecules

    2020  Volume 154, Page(s) 206–216

    Abstract: The notion that nanoscale surfaces influence protein conformational transitions stimulates the investigation of fibrillogenic polypeptides adsorbing to nanomaterials. Alpha-synuclein (αS) is a prototypical amyloidogenic protein whose aggregation is ... ...

    Abstract The notion that nanoscale surfaces influence protein conformational transitions stimulates the investigation of fibrillogenic polypeptides adsorbing to nanomaterials. Alpha-synuclein (αS) is a prototypical amyloidogenic protein whose aggregation is associated with severe neurodegenerative disorders. We explored the interaction of αS with silica nanoparticles (SNPs) in diverse solution conditions, ranging from protein-free to protein-rich media. We found that the SNP-binding region of αS, determined by site-resolved NMR spectroscopy, was similar in simple buffer and blood serum. Competition binding experiments with isotopic homologues and different proteins showed that cosolutes elicited molecular exchange in a protein-specific manner. The interaction of an oxidized, fibrillation-resistant protein form with SNPs was similar to that of unmodified αS. SNPs, however, did not stimulate fibrillation of the oxidized protein, which remained fibrillation incompetent. CD experiments revealed SNP-induced perturbations of the structural properties of oxidized and non-oxidized αS. Thus, while αS binding to SNPs is essentially orthogonal to fibril formation, the interaction perturbs the distribution of conformational states populated by the protein in the colloidal suspension. This study sheds light on the dynamic nature of αS interactions with NPs, an aspect that crucially impacts on our ability to control aggregation of αS.
    MeSH term(s) Humans ; Nanoparticles/chemistry ; Protein Aggregation, Pathological ; Protein Binding ; Protein Conformation ; Protein Folding ; Recombinant Proteins/chemistry ; Silicon Dioxide/chemistry ; alpha-Synuclein/chemistry
    Chemical Substances Recombinant Proteins ; SNCA protein, human ; alpha-Synuclein ; Silicon Dioxide (7631-86-9)
    Language English
    Publishing date 2020-03-14
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 282732-3
    ISSN 1879-0003 ; 0141-8130
    ISSN (online) 1879-0003
    ISSN 0141-8130
    DOI 10.1016/j.ijbiomac.2020.03.118
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Conformational properties of intrinsically disordered proteins bound to the surface of silica nanoparticles.

    Vitali, Michele / Rigamonti, Valentina / Natalello, Antonino / Colzani, Barbara / Avvakumova, Svetlana / Brocca, Stefania / Santambrogio, Carlo / Narkiewicz, Joanna / Legname, Giuseppe / Colombo, Miriam / Prosperi, Davide / Grandori, Rita

    Biochimica et biophysica acta. General subjects

    2018  Volume 1862, Issue 7, Page(s) 1556–1564

    Abstract: Background: Protein-nanoparticle (NP) interactions dictate properties of nanoconjugates relevant to bionanotechnology. Non-covalent adsorption generates a protein corona (PC) formed by an inner and an outer layer, the hard and soft corona (HC, SC). ... ...

    Abstract Background: Protein-nanoparticle (NP) interactions dictate properties of nanoconjugates relevant to bionanotechnology. Non-covalent adsorption generates a protein corona (PC) formed by an inner and an outer layer, the hard and soft corona (HC, SC). Intrinsically disordered proteins (IDPs) exist in solution as conformational ensembles, whose response to the presence of NPs is not known.
    Methods: Three IDPs (α-casein, Sic1 and α-synuclein) and lysozyme are compared, describing conformational properties inside HC on silica NPs by circular dichroism (CD) and Fourier-transform infrared (FTIR) spectroscopy.
    Results: IDPs inside HC are largely unstructured, but display small, protein-specific conformational changes. A minor increase in helical content is observed for α-casein and α-synuclein, reminiscent of membrane effects on α-synuclein. Frozen in their largely disordered conformation, bound proteins do not undergo folding induced by dehydration, as they do in their free forms. While HC thickness approaches the hydrodynamic diameter of the protein in solution for lysozyme, it is much below the respective values for IDPs. NPs boost α-synuclein aggregation kinetics in a dose-dependent manner.
    Conclusions: IDPs maintain structural disorder inside HC, experiencing minor, protein-specific, induced folding and stabilization against further conformational transitions, such as formation of intermolecular beta-sheets upon dehydration. The HC is formed by a single layer of protein molecules. SC likely plays a key role stabilizing amyloidogenic α-synuclein conformers.
    General significance: Protein-NP interactions can mimic those with macromolecular partners, allowing dissection of contributing factors by rational design of NP surfaces. Application of NPs in vivo should be carefully tested for amyloidogenic potential.
    MeSH term(s) Animals ; Caseins/chemistry ; Cattle ; Chick Embryo ; Circular Dichroism ; Cyclin-Dependent Kinase Inhibitor Proteins/chemistry ; Electrophoresis, Polyacrylamide Gel ; Humans ; Intrinsically Disordered Proteins/chemistry ; Muramidase/chemistry ; Nanoparticles ; Protein Binding ; Protein Conformation ; Protein Corona/chemistry ; Saccharomyces cerevisiae Proteins/chemistry ; Silicon Dioxide ; Spectroscopy, Fourier Transform Infrared ; alpha-Synuclein/chemistry
    Chemical Substances Caseins ; Cyclin-Dependent Kinase Inhibitor Proteins ; Intrinsically Disordered Proteins ; Protein Corona ; SIC1 protein, S cerevisiae ; Saccharomyces cerevisiae Proteins ; alpha-Synuclein ; Silicon Dioxide (7631-86-9) ; Muramidase (EC 3.2.1.17)
    Language English
    Publishing date 2018-04-02
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 60-7
    ISSN 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0304-4165 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    ISSN (online) 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
    ISSN 0304-4165 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    DOI 10.1016/j.bbagen.2018.03.026
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Uc I Zs.247: Show issues Location:
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