Research
Project code: PNII-RU-TE-2012-3-0227, Contract No. 37/29.04.2013
NANO-BIOSENZING OF ATHEROSCLEROSIS AND THROMBOSIS BY SURFACE ENHANCED SPATIAL OFFSET RAMAN SPECTROSCOPY (SESORS)
( http://uefiscdi.gov.ro/userfiles/file/PROIECTE%20TE%202012/CONTRACTARE%20TE%202012/TE%202012_PROIECTE%20APROBATE%20LA%20FINANTARE_CHIMIE.pdf )
Financial support from CNCS-UEFISCDI is highly acknowledged.
The objective of this project is to develop conjugated nanoparticles for nano-biosenzing of ahterosclerosis and thrombosis by means of surface enhanced spatial offset Raman spectroscopy (SESORS). Atheroscerosis and thrombosis are the major cause of morbidity, regarding cardiovascular diseases. Therefore, the understanding of their molecular structure and their interaction with biological medium. For this, combining the results of several spectroscopic methods, such as FTIR, Raman and UV-Vis, is very suitable because they give quantitative and qualitative information’s about the molecules being investigated. By functionalizing gold nanoparticles with some molecules one can get biosensors which specifically bind to desired tissue. Because heparin and C-reactive protein are binding to atherosclerotic and respectively thrombotic tissue, the conjugation of the nanoparticles with these drugs will yield nano-biosenzors which can be used for the detection of the diseases. After their fabrication, they will be tested on different tissues and on cellular cultures regarding biocompatibility and to enhance their half-life. SESORS permits to get information from obscured objects, such as deep tissue. Therefore, after the injection of the conjugated gold nanoparticles which will be used as Raman markers and drug-carriors, using the SESORS technique one can detect them in deep tissue, up to 45-50 mm. This opens the possibility for detecting diseased tissue, but also for its spatial imaging.
Team:
Dr. Szabó László , Dr. Nicolae Leopold, Dr. Vasile Chiş,Drd. István Sz. Tódor, Drd. Simon L. Botond
Objectives, Activities 2016
O1. Testing the Raman offset with functionalized gold nanoparticles in living cells. - Degree of realization: 100%A.1.1. Testing the Raman offset with functionalized gold nanoparticles in living cells selected with biological and medical experts.
A.1.2. Research and documentation internships (Austria, Germany, Hungary, France, England, Ireland, Croatia).
Ob2. SESORS in soft tissues and laboratory rats.-Degree of realization: 80%
A.2.1. Testing the Raman offset with functionalized gold nanoparticles in soft tissues selected with biological and medical experts.
A.2.2. SESORS on laboratory rats.Final results and conclusions.
Ob3. Dissemination of results. Degree of realization: 100%
A.3.1. Preliminary results have been presented at the following conferences: BIONANOSPEC 2016 Cluj-Napoca; EUCMOS 2016; European Conference on Optical Chemical Sensors and Biosensors (2016).
A.3.2. Writing and sending of a manuscript towards publication.
A.3.3. Updating the project web page.
Results 2016
R1.1. They have testing the Raman offset with functionalized gold nanoparticles in living cells. Consultation with experts and medical biologists.R1.2. A training and research documentation was performed in Germany.
R2.1. We have testing the Raman offset with functionalized gold nanoparticles in soft tissues selected with biological and medical experts.
R2.2. SESORS on laboratory rats. Final results and conclusions.
R3.1. Preliminary results have been presented at the following conferences: Conferința Naționala de Biofizica, 2-4 June 2016, Cluj Napoca, Romania etc.
R3.2. In the project, for the fourth stage 3 ISI articles have published, they have been submitted for publication a number of 4 articles in international journals (under review), respectively are being prepared a number 2 manuscripts for sending to publicate in ISI journals.
R3.3. The project webpage has been updated.
Valorization of the obtained results through participations in the following conferences:
1). Conferința Naționala de Biofizica, 2-4 June 2016, Cluj Napoca, Romania
Structural and Biological Evaluation of Heparin Reduced and Covered Gold Nanoparticles, László Szabó, István Sz. Tódor, Botond L. Simon, Loredana F. Leopold, Oana T. Marişca-Truică , Vasile Chiş, Nicolae Leopold
Poster SzaboL CNB2016 [PDF]
Oral prezentation
Conferința Naționala de Biofizica, 2-4 June 2016, Cluj Napoca, Romania
1). Raman Imaging of Dental Follicle Mesenchymal Stem Cell, Nicolae Leopold, Vasile Chiș, László Szabó
Articles published in the 2016 phase:
1). Spectroscopic and computational investigation of a thiazolidine-2,4-dione compound, I.B. Cozar, A. Pîrnău, L. Szabó, N. Vedeanu, C. Nastasă, Romanian Reports in Physics, 68(2), 630-641, (2016). [IF. 1.137]
2). Molecular Structure of Phenytoin: NMR, UV-Vis and Quantum Chemical Calculations, Luchian Raluca, Vințeler Emil, Chiș Cosmina, Vasilescu Mihai, LEOPOLD Nicolae, CHIS Vasile, Croatica Chemica Acta, 88(4), 511-526, (2016). [IF. 1.19]
3). Spectroscopic and DFT Investigation of Benzaldehyde Isonicotino – Hydrazide Compound, Cozar Ionut Bogdan, Pirnau Adrian, SZABO Laszlo, Vedeanu Nicoleta, Nastasa Cristina, Cozar Onuc, Romanian Journal Of Physics, 61(7-8), (2016). [IF. 1.398]
4). RAMAN IMAGING OF DENTAL FOLLICLE MESENCHYMAL STEM CELLS, Loredana F. Leopold, Cristina Coman, Istvan Sz. Todor, Laszlo Szabo, Olga Sorițău, Piroska Virag, Carmen M. Mihu, Vlad Moisoiu, Nicolae Leopold, STUDIA UBB PHYSICA, Vol. 60 (LX), 2, 2015, pp. 69-76 (RECOMMENDED CITATION)
Scientific report (romanian language). Raport stiintific sintetic 2013-2014-2015-2016 PNI-II-RU-TE-2012-3-0227[PDF]
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Objectives, Activities 2015
O1. Testing the viability and the biocompatibility of the gold nanoparticles. - Degree of realization: 100%A.1.1. Viability tests of gold nanoparticles functionalized with heparin and CRP. Consultation with experts and medical biologists.
A.1.2. Biocompatibility tests of gold nanoparticles functionalized with heparin and CRP. Consultation with experts and medical biologists.
A.1.3. Research and documentation internships (Austria, Germany, Hungary, France, England, Ireland, Croatia).
Ob2. Optimizing the offset Raman configuration (SORS and SESORS).-Degree of realization: 80%
A.2.1. First initial tests attempts by SORS and SESORS on viability test results obtained.
A.2.2. Improvements on gold nanoparticles functionalized after initial tests made with offset Raman configuration.
A.2.3. Research and documentation internships (Austria, Germany).
Ob3. Dissemination of results. Degree of realization: 100%
A.3.1. Preliminary results have been presented at the following conferences: ICAVS8, July 12th-17th 2015, Viena (Austria); ICMS-XIII September 9th-13th 2015, Wroclaw (Poland); PIM 2015, September 23th-25th 2015, Cluj-Napoca, Rpmania; Cluj-Napoca; 13th Romanian Conference of Medical Physics - November 7th-8th 2015, Cluj Napoca, Romania.
A.3.2. Writing and sending of a manuscript towards publication.
A.3.3. Updating the project web page.
Results 2015
R1.1. They have performed tests of viability of gold nanoparticles functionalized with heparin and CRP. Consultation with experts and medical biologists.R1.2. We started biocompatibility tests of gold nanoparticles functionalized with heparin and CRP. Consultation with experts and medical biologists.
R1.3. A training and research documentation was performed in Chemnitz, Germany.
R2.1. We made the first initial tests attempts by SORS and SESORS on viability test results obtained.
R2.2. Improvements on gold nanoparticles functionalized after initial tests made with offset Raman configuration.
R2.3. Research and documentation internships (Austria, Germany).
R3.1. Preliminary results have been presented at the following conferences: Conference on Advanced Vibrational Spectroscopy (ICAVS8), July 12th-17th 2015, Viena (Austria); XIIIth International Conference on Molecular Spectroscopy ‚,From molecules to molecular materials, biological molecular systems and nanostructures’’, September 9th-13th 2015, Wroclaw (Polonia); 10th International Conference on Processes in Isotopes and Molecules (PIM 2015), September 23th-25th 2015, Cluj-Napoca; 13th Romanian Conference of Medical Physics - November 7th-8th 2015, Cluj Napoca etc.
R3.2. In the project, for the third stage an ISI article have published, they have been submitted for publication a number of 3 articles in international journals (under review), respectively are being prepared a number 2 manuscripts for sending to publicate in ISI journals.
R3.3. The project webpage has been updated.
Valorization of the obtained results through participations in the following conferences:
1). 10th International Conference on Processes in Isotopes and Molecules (PIM 2015), September 23th-25th 2015, Cluj-Napoca, Romania
Bacteria discrimination at strain level by PCA analysis based on the SERS spectra, Nicoleta Dina, Alia Colniță, Leș Anda, Horia Baciu, Vasile Chiș, Nicolae Leopold
Poster Dina Nicoleta PIM2015 [PDF]
2). XIIIth International Conference on Molecular Spectroscopy ‚,From molecules to molecular materials, biological molecular systems and nanostructures’’, September 9th-13th 2015, Wroclaw, Poland.
UV-VIS Study of 1-(2-Pyridylazo)-2-Naphthol (PAN) and its Metal Complexes with Al(III), Mn(II), Fe(III), Cu(II) and Pb(II), Botond Lorand Simon, Laszlo Szabo, Vasile Chis
abstract Simon ICMSXIII 2015 [PDF]
3). Conference on Advanced Vibrational Spectroscopy (ICAVS8), July 12th-17th 2015, Viena, Austria.
i). Highly Sers Active Gold Nanoparticle Assemblies of Controllable Size Obtained by Heparin Reduction at Room Temperature, István Sz. Tódor, László Szabó, Oana T. Marişca, Vasile Chiș, Nicolae Leopold
Poster Todor ICAVS8 2015 [PDF]
ii). Vibrational features of dacarbazine and deticene revealed by Raman, SERS, THz-Raman and DFT methods, Alexandra Fălămaș, Mihaela Chiș, Călin Căinap, Nicolae Leopold, Vasile Chiș
Poster Chis ICAVS8 2015 [PDF]
iii). Discrimination Between Haloarchaea Genera Using Raman Spectroscopy and PCA, Anda Leș, Dina Nicoleta, Horia Baciu, Andreea Baricz, Nicolae Leopold
Poster Anda Les ICAVS8 2015 [PDF]
Oral prezentation
13th Romanian Conference of Medical Physics - November 7th-8th 2015, Cluj Napoca, Romania.
1). Evoluţia şi perspectivele fizicii medicale la Universitatea “Babeş-Bolyai" din Cluj Napoca, Vasile Chiș, Nicolae Leopold, László Szabó
2). Imagistică Raman Celulară, Nicolae Leopold, László Szabó, Vasile Chiș, István Sz. Tódor, Carmen Mihu, Vlad Moisoiu, Radu Boitor
Articles published in the 2015 phase:
1). Conformational landscape and low lying excited states of imatinib, Vinţeler Emil, Stan Nicoleta-Florina, Luchian Raluca, Căinap Călin, P. Prates Ramalho João, Chiș Vasile, Journal of Molecular Modeling, (DOI: 10.1007/s00894-015-2639-8), 21:84 (2015). [IF. 1.736]
2). Biological evaluation of hydroxylamine reduced gold nanoparticle assemblies with potential photo-thermal applications, Loredana F. Leopold, István Sz. Tódor, László Szabó, Oana T. Marişca, Vasile Chiş, Nicolae Leopold, Journal of Nanoparticle Research (under review 2015). [IF. 2.184]
3). Preparation, spectroscopic characterization and biological evaluation of heparin-reduced gold nanoparticles, László Szabó, Loredana F. Leopold, István Sz. Tódor, Botond L. Simon, Nicolae Leopold, Vasile Chiș, Jurnal of Nanoparticle Research (under review 2015). [IF. 2.184]
4). Discrimination of Haloarchaeal Genera using Raman Spectroscopy and Principal Component Analysis (PCA), Anda Leș, Nicoleta Elena Dina, Andreea Baricz, Nicolae Leopold, Horia Leonard Banciu, Journal of Biophotonics, (under review 2015). [IF. 4.447]
5). Methods and models for calculating NMR spectra: levetiracetam as a test case, Raluca Luchian, Réka-Anita Domokos, Cosmina Chiş, Mihai Vasilescu, Emil Vinţeler, Vasile Chiş, STUDIA UBB PHYSICA, Vol. 59 (LIX), 2, 2014, pp. 85-98 (RECOMMENDED CITATION)
Scientific report (romanian language). Raport stiintific sintetic 2013-2014-2015 PNI-II-RU-TE-2012-3-0227[PDF]
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Objectives, Activities 2014
O1. Gold nanoparticles synthesis. - Degree of realization: 100%A.1.1. Optimization of the gold nanoparticles model (size and shape).
A.1.2. Optimization of the heparin reduced gold nanoparticles model (size and shape).
A.1.3. Spectroscopic studies (SERS, UV-Vis, IR, AFM, TEM, SEM) used in the physical and chemical characterization of gold nanoparticles.
Ob2. Gold nanoparticles functionalization.-Degree of realization: 100%
A.2.1. Functionalization of gold nanoparticles covered by PEG/albumin, as a shell inside which heparin and C-reactive protein can be encapsulated.
A.2.2. Testing of the functionalized gold nanoparticles (encapsulated with heparin and C-reactive protein) through various spectroscopic methods (SERS, UV-Vis, IR, AFM, TEM, SEM).
A.2.3. Research and documentation internships (Austria, Germany, Hungary, France, England, Ireland, Croatia).
Ob3. Dissemination of results. Degree of realization: 100%
A.3.1. Preliminary results will be presented at the following conferences:IC-ANMBES 2014 Brasov. BIONANOSPEC 2014 Cluj-Napoca; EUCMOS 2014 Germany, SES 2014 (Chemnitz) Germany; European Conference on Optical Chemical Sensors and Biosensors, Greece (2014) etc.
A.3.2. Writing and sending of a manuscript towards publication.
A.3.3. Updating the project web page.
Results 2014
R1.1. Studies for the optimization of the gold nanoparticle model (size and shape) have been performed.R1.2. Optimization of the heparin reduced gold nanoparticle model (size and shape) has been accomplished.
R1.3. The physical and chemical characterization of gold nanoparticles has been accomplished through various spectroscopic studies (SERS, UV-Vis, IR, AFM, TEM, SEM).
R2.1. First tries in the functionalization of gold nanoparticles covered by PEG/albumin, as a shell inside which heparin and C-reactive protein can be encapsulated have been performed.
R2.2. DFT calculations (calculated IR and Raman spectra, partial atomic charges, electrostatic molecular potential, dipole and multipole moments, HOMO-LUMO orbital energy) for C-reactive protein have validated our assumptions.
R2.3. We have started the testing and encapsulation with heparin and C-reactive protein of the functionalized gold nanoparticles through various spectroscopic methods (SERS, UV-Vis, IR, AFM, TEM, SEM).
R3.1. Preliminary results have been presented at the following conferences: IC-ANMBES 2014, June 13th-15th 2014, Brasov, Romania; Surface-Enhanced Spectroscopies 2014 (SES 2014), August 7th-10th 2014, Technische Universität Chemnitz (Germany); 5th Conference on Advanced Spectroscopies on Biomedical and Nanostructured Systems (BioNanoSpec) September 7th-10th 2014, Cluj-Napoca, Romania.
R3.2. For the second stage of the project, three scientific papers have been sent to publication in ISI rated journals.
R3.3. The project webpage has been updated.
Valorization of the obtained results through participations in the following conferences:
1). The Third International Conference on Analytical and Nanoanalytical Methods for Biomedical and Environmental Sciences “IC-ANMBES 2014” June 13th-15th 2014, Brasov, Romania.
poster_ANMBES_bacterii_2014 [PDF]
2). Surface-Enhanced Spectroscopies 2014 (SES 2014), August 7th-10th 2014, Technische Universität Chemnitz (Germany).
poster_SES_Chemnitz_2014 [PDF]
3). 5th Conference on Advanced Spectroscopies on Biomedical and Nanostructured Systems (BioNanoSpec) September 7th-10th 2014, Cluj-Napoca, Romania.
poster_Szabo_Bionanospec_2014 [PDF]
poster_Boitor_Bionanospec_2014 [PDF]
poster_Simon_Bionanospec_2014 [PDF]
Articles published in the 2014 phase:
1). ADSORPTION OF SULFAMETHOXAZOLE MOLECULE ON SILVER COLLOIDS: A JOINT SERS AND DFT STUDY, Alia Ungurean, Mircea Oltean, Leontin David, Nicolae Leopold, João P. Prates Ramalho , Vasile Chis, Journal of Molecular Structure 1073 (2014) 71–76. [IF. 1.599]
2). GOLD NANOPARTICLE ASSEMBLIES OF CONTROLLABLE SIZE OBTAINED BY HYDROXYLAMINE REDUCTION AT ROOM TEMPERATURE, István Sz. Tódor, László Szabó, Vasile Chiş, Oana T. Marișca, Nicolae Leopold, Jurnal of Nanoparticle Research, 16(12), (2014). [IF. 2.278]
3). SPECTROSCOPIC AND COMPUTATIONAL INVESTIGATION OF A THIAZOLIDINE-2,4-DIONE DERIVATIVE, I.B. Cozar, A. Pîrnău, L. Szabó, N. Vedeanu, C. Nastasă, Romanian Reports în Physics, (In Press: Volume 67, Number 4, 2015). [IF. 1.137]
Scientific report (romanian language). Raport stiintific sintetic 2013-2014 PNI-II-RU-TE-2012-3-0227[PDF]
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Objectives, Activities 2013
O1. The physicochemical characterization of the heparin molecule. - Degree of realization: 100%A.1.1. Spectroscopic investigation of heparin through FTIR, Raman, FT-Raman, SERS and UV-Vis spectroscopy.
A.1.2. Spectroscopic investigation of heparin at different pH values, with different solvents.
A.1.3. DFT calculations: calculated IR and Raman spectra, partial atomic charges, electrostatic molecular potential,dipole and multipole moments, HOMO-LUMO orbital energy for heparin.
A.1.4. Interpretation of DFT calculations regarding the adsorption geometry and possible bonding locations. Correlations with experimantal data.
Ob2. The physicochemical characterization of the C-reactive protein.-Degree of realization: 100%
A.2.1. Spectroscopic investigation of C-reactive protein through FTIR, Raman, FT-Raman, SERS and UV-Vis spectroscopy at different pH values, with different solvents.
A.2.2. DFT calculations: calculated IR and Raman spectra, partial atomic charges, electrostatic molecular potential, dipole and multipole moments, HOMO-LUMO orbital energy for C-reactive protein.
A.2.3. Research and documentation internships (Austria, Germany, Hungary, France, England, Ireland, Croatia).
Ob3. Dissemination of results. Degree of realization: 100%
A.3.1. Presentation of preliminary results at the following conferences: BIONANOSPEC Cluj-Napoca; XIIth International Conference on Molecular Spectroscopy, Poland; 15th ECSBM - Oxford, United Kingdom; The 5th National Conference of Applied Physics, CNFA 2013, Iasi, Romania. etc.
A.3.2 Preparation and submission for publication of a manuscript regarding the theoretical caracterization and the physicochemical experimental characterization of heparin and of C-reactive protein.
A.3.3. Updating the project web page.
Results 2013
R1.1. Spectroscopic investigation of heparin through FTIR, Raman, FT-Raman, SERS and UV-Vis spectroscopy has been carried out.R1.2. Spectroscopic investigation of heparin at different pH values, with different solvents has been performed.
R1.3. DFT calculations: calculated IR and Raman spectra, partial atomic charges, electrostatic molecular potential, dipole and multipole moments, HOMO-LUMO orbital energy for heparin.
R1.4. A correlation with experimantal data has been developed through the interpretation of DFT calculations regarding the adsorption geometry and possible bonding locations.
R2.1. We inferred a number of physicochemical properties of C-reactive protein through spectroscopic investigation (through FTIR, Raman, FT-Raman, SERS and UV-Vis spectroscopy at different pH values, with different solvents).
R2.2. DFT calculations (calculated IR and Raman spectra, partial atomic charges, electrostatic molecular potential, dipole and multipole moments, HOMO-LUMO orbital energy) for C-reactive protein have validated our assumptions.
R2.3. Research for the synthesis of gold nanoparticles reduced by heparin has begun.
R3.1. Preliminary results have been presented at the following conferences: XIIth International Conference on Molecular Spectroscopy, Poland; The 5th National Conference of Applied Physics, CNFA 2013, Iasi, România; Conferinţa Internaţională de Fizică TIM 13 - Timişoara, România.
R3.2. In the first stage of the project, three articles have been submited for publication in ISI rated papers.
R3.3. The project webpage has been updated.
Valorization of the obtained results through participations in the following conferences:
1). XIIth International Conference on Molecular Spectroscopy. From Molecules to Nano- and Biomaterials, Kraków – Białka Tatrzańska 8 – 12 September 2013 Polonia. Poster ICMS 2013 [PDF]
2). The 5th National Conference of Applied Physics, CNFA 2013, 23-24 May 2013 Iasi, România. Poster CNFA 2013 [PDF]
3). Conferinţa Internaţională de Fizică TIM 13, 21-24 noiembrie 2013 - Timişoara, România. TISz_poster_TIM2013 [PDF]
SBL_poster_TIM2013 [PDF]
Articles published in the 2013 phase:
1). Towards a Receptor-free Immobilization and SERS Detection of Urinary Tract Infections Causative Pathogens, Nicoleta E. Mircescu, Haibo Zhou, Nicolae Leopold, Vasile Chiş, Natalia P. Ivleva, Reinhard Niessner, Andreas Wieser, Christoph Haisch, Analytical and Bioanalytical Chemistry, 406 (13), (2014) 3051-3058. [IF. 3.659]
2). Surface-enhanced Raman scattering and DFT investigation of 1,5-diphenylcarbazide and its metal complexes with Ca(II), Mn(II), Fe(III) and Cu(II), László Szabó, Krisztian Herman, Nicoleta Elena Mircescu, István Szabolcs Tódor, Simon Botond Lorand, Radu Alex Boitor, Nicolae Leopold, Vasile Chiş, Journal of Molecular Structure, 1073, (2014) 10-17. [IF. 1.599]
3). Anisotropic gold nanoparticles synthesized at room temperature using collagen, Oana T. Marișca, Nicolae Leopold, Journal of Nanoparticle Research, (submitted November 2015). [IF. 2.278].
Scientific report (romanian language). Raport stiintific 2013 PNI-II-RU-TE-2012-3-0227 [PDF]
