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Development of a fluorescent nanosensor from the electrospinning of PVA and graphene quantum dots: application in the detection of Alzheimer's biomarkers

Grant number: 15/08523-8
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): July 01, 2015
Effective date (End): November 30, 2016
Field of knowledge:Engineering - Materials and Metallurgical Engineering - Nonmetallic Materials
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Anderson de Oliveira Lobo
Grantee:Bruno Vinícius Manzolli Rodrigues
Home Institution: Instituto de Pesquisa e Desenvolvimento (IP&D). Universidade do Vale do Paraíba (UNIVAP). São José dos Campos , SP, Brazil
Associated research grant:11/17877-7 - Development of new polymeric scaffolds by electrospinning technique with incorporation of vertically aligned carbon nanotubes and nanohidroxyapatite for bone tissue regeneration, AP.JP


Alzheimer's disease (AD), a chronic neurodegenerative disease, is the most common form of dementia and affects more than 44 million of people in the World and more than 1 million only in Brazil. The diagnosis of AD in a very early stage is extremely necessary and desirable, since it is incurable and it worsens progressively until death. In order to estimate the risk or presence of this disease, AD's biomarkers, such as beta amyloid and ApoE4, are neurochemical indicators that can be detected in some physiological fluids such as CSF (cerebrospinal fluid), serum and plasma. However, up to date, the current methods of AD's biomarkers detection in such fluids do not present high sensitivity for early diagnosis and the costs are incompatible with the needed large screening. In this context, we propose the development and optimization of a fluorescent nanosensor based on the electrospinning of poly (vinyl alcohol) (PVA) and water-soluble graphene quantum dots (GQDs) on ITO coated glass slides, for detection of AD's biomarkers based on the fluorescence quenching of the GQDs. Given the three-dimensional and porous structure of the electrospun membrane and its high surface area to volume ratio, it is expected a high diffusion and adsorption of the AD's biomarkers. Blue photoluminescent GQDs will be prepared by incomplete carbonization of citric acid followed by dispersion in alkaline solution. GQDs afford in their structures carboxyl functional groups suitable for immobilization of antibodies, allowing an enhanced efficiency in the capturing and pre-concentrating of AD's biomarkers. The best conditions for electrospinning will be investigated considering the (inter)combination of different experimental parameters such as polymer and GQDs concentration; applied voltage; needle-collector distance and solution flow rate. The antibodies will be linked to the GQDs by peptide bonding between the amino groups from the Lys residues and the carboxyl groups from the GQDS, by using [N-(3-dimethylamino)propyl]-N-ethylcarbodiimide (EDC) previously activated with N-hydroxysulfosuccinimide (Sulfo-NHS). The structure and fluorescence properties of the PVA/GQDs hybrid membranes will be evaluated using fluorescence, scanning and transmission microscopies, as well as other relevant techniques of materials characterization. The developed nanodevice will be also tested in real clinical CSF, plasma and serum samples of patients who suffer from AD, aiming at the detection of beta amyloid and ApoE4. It is expected to obtain a high sensitive nanodevice for AD's biomarkers detection in order to diagnose this disease in a very early stage, as well as to provide reliable measures of its progress. (AU)

Scientific publications (15)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MACHADO-PAULA, M. M.; CORAT, M. A. F.; LANCELLOTTI, M.; MI, G.; MARCIANO, F. R.; VEGA, M. L.; HIDALGO, A. A.; WEBSTER, T. J.; LOBO, A. O. A comparison between electrospinning and rotary-jet spinning to produce PCL fibers with low bacteria colonization. Materials Science & Engineering C-Materials for Biological Applications, v. 111, JUN 2020. Web of Science Citations: 0.
RODRIGUES, BRUNO V. M.; CABRAL, TAYNA S.; SGOBBI, LIVIA F.; DELEZUK, JORGE A. M.; PESSOA, RODRIGO S.; TRIBONI, EDUARDO R.; DE MORAES, THAISA B. F.; LOBO, ANDERSON O. A simple and green method for the production of nanostructured materials from poly(vinyl alcohol)/graphene quantum dots. Materials Chemistry and Physics, v. 219, p. 242-250, NOV 1 2018. Web of Science Citations: 2.
PESSOA, R. S.; DOS SANTOS, V. P.; CARDOSO, S. B.; DORIA, A. C. O. C.; FIGUEIRA, F. R.; RODRIGUES, B. V. M.; TESTONI, G. E.; FRAGA, M. A.; MARCIANO, F. R.; LOBO, A. O.; MACIEL, H. S. TiO2 coatings via atomic layer deposition on polyurethane and polydimethylsiloxane substrates: Properties and effects on C. albicans growth and inactivation process. Applied Surface Science, v. 422, p. 73-84, NOV 15 2017. Web of Science Citations: 10.
SGOBBI, LIVIA F.; ZIBORDI-BESSE, LARISSA; RODRIGUES, BRUNO V. M.; RAZZINO, CLAUDIA A.; DA SILVA, JUAREZ L. F.; MACHADO, SERGIO A. S. Polyhydroxamicalkanoate as a bioinspired acetylcholinesterase-based catalyst for acetylthiocholine hydrolysis and organophosphorus dephosphorylation: experimental studies and theoretical insights. CATALYSIS SCIENCE & TECHNOLOGY, v. 7, n. 15, p. 3388-3398, AUG 7 2017. Web of Science Citations: 1.
RODRIGUES, BRUNO V. M.; RAZZINO, CLAUDIA A.; OLIVEIRA, FRANCILIO DE CARVALHO; MARCIANO, FERNANDA R.; LOBO, ANDERSON O. On the design and properties of scaffolds based on vertically aligned carbon nanotubes transferred onto electrospun poly (lactic acid) fibers. MATERIALS & DESIGN, v. 127, p. 183-192, AUG 5 2017. Web of Science Citations: 3.
SANTANA-MELO, GABRIELA F.; RODRIGUES, BRUNO V. M.; DA SILVA, EDMUNDO; RICCI, RITCHELLI; MARCIANO, FERNANDA R.; WEBSTER, THOMAS J.; VASCONCELLOS, LUANA M. R.; LOBO, ANDERSON O. Electrospun ultrathin PBAT/nHAp fibers influenced the in vitro and in vivo osteogenesis and improved the mechanical properties of neoformed bone. COLLOIDS AND SURFACES B-BIOINTERFACES, v. 155, p. 544-552, JUL 1 2017. Web of Science Citations: 15.
STOCCO, T. D.; RODRIGUES, B. V. M.; MARCIANO, F. R.; LOBO, A. O. Design of a novel electrospinning setup for the fabrication of biomimetic scaffolds for meniscus tissue engineering applications. Materials Letters, v. 196, p. 221-224, JUN 1 2017. Web of Science Citations: 15.
SILVA, EDMUNDO; REIS DE VASCONCELLOS, LUANA MAROTTA; RODRIGUES, BRUNO V. M.; DOS SANTOS, DANILO MARTINS; CAMPANA-FILHO, SERGIO P.; MARCIANO, FERNANDA ROBERTA; WEBSTER, THOMAS J.; LOBO, ANDERSON OLIVEIRA. PDLLA honeycomb-like scaffolds with a high loading of superhydrophilic graphene/multi-walled carbon nanotubes promote osteoblast in vitro functions and guided in vivo bone regeneration. Materials Science & Engineering C-Materials for Biological Applications, v. 73, p. 31-39, APR 1 2017. Web of Science Citations: 12.
TONIATTO, T. V.; RODRIGUES, B. V. M.; MARSI, T. C. O.; RICCI, R.; MARCIANO, F. R.; WEBSTER, T. J.; LOBO, A. O. Nanostructured poly (lactic acid) electrospun fiber with high loadings of TiO2 nanoparticles: Insights into bactericidal activity and cell viability. Materials Science & Engineering C-Materials for Biological Applications, v. 71, p. 381-385, FEB 1 2017. Web of Science Citations: 16.
PEREIRA, F. A. S.; SALLES, G. N.; RODRIGUES, B. V. M.; MARCIANO, F. R.; PACHECO-SOARES, C.; LOBO, A. O. Diamond nanoparticles into poly(lactic acid) electrospun fibers: Cytocompatible and bioactive scaffolds with enhanced wettability and cell adhesion. Materials Letters, v. 183, p. 420-424, NOV 15 2016. Web of Science Citations: 6.
GRANATO, ALESSANDRO E. C.; RODRIGUES, BRUNO V. M.; RODRIGUES-JUNIOR, DORIVAL M.; MARCIANO, FERNANDA R.; LOBO, ANDERSON O.; PORCIONATTO, MARIMELIA A. Magnetic super-hydrophilic carbon nanotubes/graphene oxide composite as nanocarriers of mesenchymal stem cells: Insights into the time and dose dependences. Materials Science & Engineering C-Materials for Biological Applications, v. 67, p. 694-701, OCT 1 2016. Web of Science Citations: 4.
ZANIN, HUDSON; MANZOLLI RODRIGUES, BRUNO VINICIUS; RIBEIRO NETO, WILSON ALVES; SUMAN BRETAS, ROSARIO ELIDA; DA-SILVA, NEWTON SOARES; MARCIANO, FERNANDA ROBERTA; LOBO, ANDERSON OLIVEIRA. High loading of graphene oxide/multi-walled carbon nanotubes into PDLLA: A route towards the design of osteoconductive, bactericidal and non-immunogenic 3D porous scaffolds. Materials Chemistry and Physics, v. 177, p. 56-66, JUL 1 2016. Web of Science Citations: 4.
RODRIGUES, BRUNO V. M.; SILVA, ALINE S.; MELO, GABRIELA F. S.; VASCONSCELLOS, LUANA M. R.; MARCIANO, FERNANDA R.; LOBO, ANDERSON O. Influence of low contents of superhydrophilic MWCNT on the properties and cell viability of electrospun poly (butylene adipate-co-terephthalate) fibers. Materials Science & Engineering C-Materials for Biological Applications, v. 59, p. 782-791, FEB 1 2016. Web of Science Citations: 27.
DE CASTRO, JUCARA G.; RODRIGUES, BRUNO V. M.; RICCI, RITCHELLI; COSTA, MAIRA M.; RIBEIRO, ANDRE F. C.; MARCIANO, FERNANDA R.; LOBO, ANDERSON O. Designing a novel nanocomposite for bone tissue engineering using electrospun conductive PBAT/polypyrrole as a scaffold to direct nanohydroxyapatite electrodeposition. RSC ADVANCES, v. 6, n. 39, p. 32615-32623, 2016. Web of Science Citations: 22.
RODRIGUES, BRUNO V. M.; LEITE, NELLY C. S.; CAVALCANTI, BRUNO DAS NEVES; DA SILVA, NEWTON S.; MARCIANO, FERNANDA R.; CORAT, EVALDO J.; WEBSTER, THOMAS J.; LOBO, ANDERSON O. Graphene oxide/multi-walled carbon nanotubes as nanofeatured scaffolds for the assisted deposition of nanohydroxyapatite: characterization and biological evaluation. INTERNATIONAL JOURNAL OF NANOMEDICINE, v. 11, p. 2569-2585, 2016. Web of Science Citations: 16.

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