Nanoterapia fototermica selectiva a hepatocarcinomului prin
Nanoterapia fototermica selectiva a hepatocarcinomului prin
Nanoterapia fototermica selectiva a hepatocarcinomului prin
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Coordonator: Universitatea de Medicina si<br />
Farmacie ―Iuliu Hatieganu‖ Cluj-Napoca<br />
Director proiect: Conf. Dr. Iancu Cornel<br />
Catedra Chirurgie 3 Cluj-Napoca
Parteneri în consorţiu:<br />
• P1. Spitalul Clinic de Urgenta Prof. Dr. ―Octavian Fodor‖<br />
Cluj-Napoca<br />
• P2. Institutul Naţional de Cercetare-Dezvoltare pentru<br />
Tehnologii Izotopice şi Moleculare Cluj-Napoca<br />
• P3 Universitatea de Stiinte Agricole si Medicina<br />
Veterinara Cluj Napoca<br />
• P4 Institutul Inimii Nicolae Stancioiu Cluj-Napoca<br />
• P5 Nanotechnology Center at University of Arkansas at<br />
Little Rock, SUA<br />
Buget: 2.000.000 RON<br />
Adresa web: http://clinicachirurgie3.ro/nanohep
Obiectivele specifice caractere de originalitate:<br />
• Identificarea target-urilor membranare specifice in scopul dirijarii<br />
selective a nanotubulilor de carbon la nivelul celulelor maligne<br />
hepatice<br />
• Functionalizarea (legarea) nanotuburilor de carbon cu elemente<br />
complementare (anticorpi) target-urilor neoplazice hepatice<br />
specifice identificate.<br />
• Cercetarea potentialului tumoricid al iradierii LASER in vitro asupra<br />
celulelo hepatice tumorale continand CNT internalizate<br />
• Identificarea modalitatilor practice de administrare a CNT<br />
functionalizate si marcate specific in organismul gazda<br />
Beneficiarii rezultatelor:<br />
• pacientii cu carcinom hepatocelular<br />
• personalul medical<br />
• cercetatori, ingineri,<br />
• studenti<br />
• agenti economici
• Buget de stat: 130000 RON<br />
• Precursori/rezultate intermediare Etapa 1<br />
• Infiintarea Societatii Romane de Nanomedicina<br />
• Infiintarea si dotarea Centrului de Cercetari in Nanomedicina al<br />
UMF Cluj-Napoca si Spitalului Clinic O. Fodor (5 incaperi<br />
insumand 110 m2)<br />
• Cereri de brevet:<br />
• Attorney Docket No. 999084B (07.10.2008) TITLE OF<br />
INVENTION: ―Metallic nanoparticles coated with graphitic shells<br />
as localized radio frequency absorbers for cancer therapy‖<br />
INVENTOR NAMES: Alexandru S. Biris, Yang Xu, Zhongrui Li,<br />
Meena Mahmood, and Alexandru R. Biris (brevet uspto)<br />
• Cererea de brevet cu titlul: ―Procedeu de determinare a<br />
sulfamidelor din muşchi de pasăre <strong>prin</strong> extracţie dispersivă în<br />
fază solidă folosind nanotuburi de carbon de tip<br />
MWCNT‖.Autori :Bele Constantin, Matea Cristian Tudor, Dan<br />
Lupu, Alexandru Biriş, Iancu Cornel, Mocan Lucian. (brevet<br />
OSIM:125476 A2 din 19.09.2008)
•Precursori/rezultate<br />
intermediare Etapa 1<br />
• Studii de interes national:<br />
• Studiu privind prelevarea, cultivarea si intretinerea celulelor maligne<br />
hepatice<br />
• Studiu privind realizarea xenogrefelor de hepatocarcinom uman la<br />
soarecii imunodeprimati <strong>prin</strong> implantare de tesuturi tumorale de la<br />
pacienti<br />
• Studiu privind functionalizarea (legarea) nanotuburilor de carbon cu<br />
anticorpi specifici pentru membrana celulelor tumorale hepatice cu rol in<br />
targeting celular<br />
• Studiu privind nanofototermoliza LASER a celulelor maligne marcate cu<br />
anticorpi<br />
• Studiu privind administrarea si testarea in vivo a noilor materiale<br />
nanobiocompozite cu rol antineoplazic<br />
• Prezentari la conferinte internationale (sept 2008-feb 2009): 6<br />
• Stagii de perfectionare in strainatate pentru tineri doctoranzi pe tema<br />
proiectului: 3
Echipamente Cercetare-UMF Cluj<br />
1 Vortex –agitator magnetic<br />
Fact 9202103/<br />
03.10.2008<br />
1799.07<br />
2 Lampa laser Fact 58/ 14.04.2008 21003.50<br />
3 Distilator<br />
Fact 9203323/<br />
19.11.2008<br />
1799.98<br />
4<br />
Aparat sectionare tesuturi cu Fact 0012733/<br />
ultrasunete<br />
30.10.2008<br />
31951.5<br />
5 Ph-metru de laborator<br />
Fact 9202723/<br />
30.10.2008<br />
1798.79<br />
5 Baie de apa termostatata cu accesorii<br />
Fact 9203334/<br />
20.11.2008<br />
14778.24<br />
6 Balanta Kern<br />
Fact 9202722/<br />
30.10.2008<br />
1799.04<br />
Echipamente Cercetare-P1 SCUCN Cluj<br />
7 Centrifuga de racire HETTICH<br />
Fact 9202091/<br />
03.10.2008<br />
15.551,91<br />
8 Masina pt. spalat sticlarie MIELE<br />
Fact 1359/<br />
13.10.2008<br />
15.562,88<br />
9 Microscop model AE-31<br />
Fact 9202709/<br />
30.10.2008<br />
11.715,67
Stagiu de pregatire 07.09.2008-06.10.2008 pentru 3 doctoranzi ai UMF Iuliu Hatieganu la Centrul<br />
de Nanotehnologii al Universitatii Little Rock, SUA,.<br />
4 teme de doctorat in domeniul terapiei tintite molecular a cancerelor utilizand nanotuburi specific<br />
functionalizate:<br />
“<strong>Nanoterapia</strong> in cancerele digestive- modele experimentale.”-<br />
drd. Mocan Lucian<br />
“Implicatiile stresului oxidativ in relatie cu nanomaterialele”<br />
drd.Mocan Teodora<br />
“Functionalizarea nanotuburilor de carbon cu aplicatii in nanomedicina”<br />
drd. Simon Stefania<br />
“Sinteza nanoparticulelor cu aplicatii in terapia cancerelor”<br />
drd. Matea Cristian<br />
Alti doctoranzi participanti acitiv in proiect: Drd. Iancu Dana, Zaharie Florin, Mihaileanu<br />
Florin<br />
Studenti participanti activ in proiect: Fustos Tiberiu, Iorga Otilia, Cozar Octavian, Hossu<br />
Miana (participanti la 2 conferinte internationale studentesti pe tema proiectului Novi<br />
Sad, Berlin)<br />
<br />
Cuantumul salariilor la tinerii sub 35 de ani 67.2% (din totalul bugetului alocat pe salarii)
• Buget de stat: 65000<br />
• Precursori/rezultate intermediare<br />
• Publicatii ISI in extenso in jurnale din strainatate cu factor de impact: 8<br />
• Prezentari la conferinte internationale cu tema proiectului (cu abstracte publicate in jurnale<br />
ISI): 4<br />
• Capitol de carte publicat de o editura internationala: Bele Constantin ( autor) ‖Carbon<br />
Nanotubes as a New Solid Phase Extraction Sorbent for Analysis of Environmental<br />
Pollutants ― , capitol în ― Carbon Nanotubes ― ( editor Vedran Kordic ) , la editura IN-TECH,<br />
Vienna, Austria , ISBN 978-953-7619<br />
• Dotarea Centrului de Cercetari in Nanomedicina<br />
• Investitii in echipamente de cercetare: 17000 RON<br />
1<br />
ECHIPAMENTE CD CO UMF<br />
Hota<br />
microbiologica<br />
Fact<br />
9206408/06.08.2009 17000
• Buget de stat: 262245<br />
• Publicatii ISI in extenso in jurnale din strainatate cu factor de impact: 4<br />
• Publicatii ISI (in press) in extenso in jurnale din strainatate cu factor de impact: 1<br />
• Publicatii ISI (sub review extern) in extenso in jurnale din strainatate cu factor de impact:3<br />
• Prezentari la conferinte internationale cu tema proiectului publicate in abstract: 6<br />
• Capitol de carte publicat de o editura internationala: Cornel Iancu ( author) ‖ Human Cord Blood-Derived Stem Cells in<br />
Transplantation and Regenerative Medicine― , capitol în "Stem Cells", ISBN 978-953-307-232-6., la editura IN-TECH, Vienna,<br />
Austria, in press<br />
<br />
<br />
<br />
Cerere brevet:Cerere de brevet OSIM cu nr. a1157/2010 cu titlul :Procedeu de obţinere a nanotuburilor de carbon de tip MWCNT<br />
funcţionalizate, ultra-scurte <strong>prin</strong> oxidare controlata.Autori :Matea Cristian Tudor, Bele Constantin, Iancu Cornel, Mocan Lucian, Orza<br />
Anamaria-Ioana<br />
Propunere FP7-Euronanomed 2-nd call, 11 iunie 2010 (Coordonator UMF Cluj-Dr. Iancu Cornel, Parteneri: USAMV Cluj, Ben Gurion<br />
University, Nejev Israel, Ikerlat Polymers, Spania): Selective targeted necrosis of liver cancer using radiofrequency activated bioligand<br />
nanocompounds.<br />
Modele experimentale noi din punct de vedere stiintific:<br />
‣ Model experimental de functionalizare a nanotuburilor de carbon cu albumina serica umana<br />
‣ Model experimental de tratament in vitro al carcinomului hepatocelular <strong>prin</strong> administrare de nanotuburi de carbon functionalizate cu<br />
albumina serica umana combinate cu iradiere laser externa<br />
•
Lista cu lucrări ştiinţifice publicate in reviste cotate 2009<br />
1. Cornel Iancu, Ioana R. Ilie, Carmen E. Georgescu, Razvan Ilie, Alexandru R. Biris, Teodora Mocan, Lucian C. Mocan,<br />
Florin Zaharie, Dana Todea-Iancu, Sergiu Susman, Dan Rus Ciuca, Alexandru S. Biris. ―Applications of Nanomaterials in Cell<br />
Stem Therapies and the Onset of Nanomedicine‖. Particulate Science and Technology, 2009, 27: 6, 562 — 574<br />
2. Mahmood M, Karmakar A, Fejleh A, Mocan T, Iancu C, Mocan L, Iancu DT, Xu Y,Dervishi E, Li Z, Biris AR, Agarwal R, Ali<br />
N, Galanzha EI, Biris AS, Zharov VP. Synergistic enhancement of cancer therapy using a combination of carbon nanotubes<br />
and anti-tumor drug. Nanomed. 2009 Dec;4(8):883-93 (Impat Factor 6.7)<br />
3. C. Bele, C.T. Matea , M. MorarRomanian Journal of Biochemistry , vol. 46, ISSN 1582-3318, p.118-19 Fuctionalized<br />
single walled nanotubes as a new solid phase microextraction sorbent for analysis of food preservatives<br />
4. C. T. Matea, C. Bele, M. Morar Romanian Journal of Biochemistry , vol. 46, ISSN 1582-3318, p. 120-121 Carbon<br />
nanotubes as solid phase micro-extraction sorbent for the determination of benzene in urine<br />
5. Li Z, Kunets VP, Saini V, Xu Y, Dervishi E, Salamo GJ, Biris AR, Biris AS. Light-harvesting using high density p-type<br />
single wall carbon nanotube/n-type silicon heterojunctions. ACS Nano. 2009 Jun 23;3(6):1407-14. (Impat Factor 7.5)
Publicatii ISI 2009<br />
6. E. Dervishi, Z. Li, Y. Xu, V. Saini, A.R. Biris, D. Lupu, A.S. Biris, „Carbon Nanotubes: Synthesis, Properties, and<br />
Applications‖, Particul. Sci. Technol., 27(2), 107-125, 2009.<br />
7. E. Dervishi, Z. Li, F. Watanabe, Y. Xu, V. Saini, A. R. Biris, A. S. Biris, ―Thermally controlled synthesis of single-wall<br />
carbon nanotubes with selective diameters‖, J. Mater. Chem., 19(19), 3004-30012, 2009.<br />
8. E. Dervishi, Z. Li, Y. Xu, V. Saini, F. Watanabe, A.R. Biris, A. Bonpain, J.J. Garbay, A. Meriet, M. Richard, A.S. Biris,<br />
―The influence of Fe-Co/MgO Catalyst composition on the growth properties of carbon nanotubes‖, Particul. Sci.<br />
Technol., 27(3), 222-237, 2009.<br />
9. Dervishi E, Li Z, Watanabe F, Biswas A, Xu Y, Biris AR, Saini V, Biris AS. Large-scale graphene production by RFcCVD<br />
method. Chem Commun (Camb). 2009 Jul 21;(27):4061-3.<br />
10.
Publicatii ISI cu factor de impact 2010<br />
1. Xu Y, Mahmood M, Fejleh A, Li Z, Watanabe F, Trigwell S, Little RB, Kunets VP, Dervishi E, Biris AR, Salamo<br />
GJ, Biris AS. Carbon-covered magnetic nanomaterials and their application for the thermolysis of cancer cells.<br />
Int J Nanomedicine. 2010 Apr 7;5:167-76. (IF:3)<br />
2. Mahmood M, Casciano DA, Mocan T, Iancu C, Xu Y, Mocan L, Iancu DT, Dervishi E, Li Z, Abdalmuhsen M,<br />
Biris AR, Ali N, Howard P, Biris AS. Cytotoxicity and biological effects of functional nanomaterials delivered to<br />
various cell lines. J Appl Toxicol. 2010 Jan;30(1):74-83. (IF:2.2)<br />
3. Yang Xu, Alokita Karmakar, Daoyuan Wang, Meena W. Mahmood, Fumiya Watanabe, Yongbin Zhang, Ashley<br />
Fejleh, Phillip Fejleh, Zhongrui Li, Ganesh Kannarpady, Syed Ali, Alexandru R. Biris, Alexandru S. Biris<br />
Multifunctional Fe3O4 Cored Magnetic-Quantum Dot Fluorescent Nanocomposites for RF Nanohyperthermia<br />
of Cancer Cells The Journal of Physical Chemistry C 2010 114 (11), 5020-5026 (IF:3.6)<br />
4. Alexandru Radu Biris, Enkeleda Dervishi, Stefania Simon, Dan Lupu, Ioan Misan, Cornel Iancu, Simona Valeria<br />
Clichici, Yang Xu, Fumia Watanabe, Alexandru Sorin Biris, Analytic studies of high quality singlewall carbon<br />
nanotubes synthesized on a novel Fe:Mo:MgO catalyst, Physica E: Low-dimensional Systems and<br />
Nanostructures, Volume 43, Issue 1, November 2010, Pages 552-558, ISSN 1386-9477
Publicatii ISI cu factor de impact 2010 in press/sub review extern<br />
1. Iancu C, Mocan L, Bele C, Orza A, Tabaran F., Catoi C, Stiufiuc R, Stir A, Matea C, Iancu D, Agoston-Coldea<br />
L, Zaharie F, Mocan T., Carbon nanotube-enhanced laser thermal ablation for the destruction of liver cancer cells in<br />
vitro by specific delivery of multi-walled carbon nanotubes (MWCNT) functionalized with human serum<br />
albumin (HSA), Int J Nanomed. In Press. (IF=2.8)<br />
2. “Ex vivo photothermal ablation of human pancreatic cancer with albumin functionalized multi-walled carbon nanotubes.”,<br />
written by Mocan L, Tabaran F, Stiufiuc R, Bele C, Lucan C, Catoi C, Matea C, Iancu D, Zaharie F, Vlad L, Mocan T, Iancu C<br />
submitted to ACS Nano IF: 7.5 (sub review extern, Manuscript ID: nn-2010-020538)<br />
3. Simon, Stefania; Rada Ilie, Ioana; Dervishi, Enkeleda; Xu, Yang; Biris, Alexandru; Biris, Alexandru; Mocan, Teodora;<br />
Mocan, Lucian; Todea Iancu, Dana; Iancu, Cornel; Misan, Ioan; Lupu, Dan; Li, Zhongrui; Biswas, Abhijit"Studies on Near<br />
Infrared Optical Absorption, Raman Scattering and Corresponding Thermal Properties of Single- And Double-Walled Carbon<br />
Nanotubes for Possible Cancer Targeting and Laser-Based Ablation“ submitted to The Journal of Physical Chemistry<br />
(IF:2.7),(sub review extern- Manuscript ID: jp-2010-10110u)<br />
4. Mocan L, Agoston L, Bele C, Stiufiuc R, Mocan T, Iancu C "Genotoxicity of nanomaterials with applications in cancer<br />
research. Nanoscale, IF 4.2 (sub review extern Manuscript ID is NR-REV-04-2010-000271.
Lista cu lucrări prezentate la manifestari stiintifice participare internationala<br />
2008<br />
1. A.S. Biris, Z. Li, Y. Xu, V. Saini, E. Dervishi, R. Sharma, S. Trigwell, F. Watanabe, M.K. Mazumder, A.R. Biris, D.<br />
Lupu, ―Multifunctional Coating with Carbon Nanotubes for Electrostatic Mitigation and Their Formation by Laser Heating‖, IEEE<br />
Annual Meeting, Industrial Aplication Society, Edmonton, Canada, October 2008.<br />
2. A. Biris, T. Mocan “Cytotoxicity of Carbon Nanomaterials: Single-Wall Nanotube, Multi-Wall Nanotube‖, CANCER<br />
TARGETING BY NANOMATERIALS, MIAMI, FLORIDA, 25-29 SEPTEMBRIE, 2008<br />
3. A. Biris, D.Todea-Iancu, ―Interactions of Nanomaterials with Biological Systems‖, CANCER TARGETING BY NANOMATERIALS,<br />
MIAMI, FLORIDA, 25-29 SEPTEMBRIE, 2008<br />
4. D.Todea-Iancu, ―Optimal nanomaterial administration methods for human cancer treatment‖, CANCER TARGETING BY<br />
NANOMATERIALS, MIAMI, FLORIDA, 25-29 SEPTEMBRIE, 2008<br />
5. T. Mocan , ―Selectivity optimization of nanotargeting the pancreatic cancer cells‖, CANCER TARGETING BY NANOMATERIALS,<br />
MIAMI, FLORIDA, 25-29 SEPTEMBRIE, 2008<br />
6. L.Mocan, A. Biris ―Nanotherapy in pancreatic cancer, experimental models‖, CANCER TARGETING BY NANOMATERIALS,<br />
MIAMI, FLORIDA, 25-29 SEPTEMBRIE, 2008
• Prezentari la congrese internationale:( publicatii in abstract in reviste indexate ISI)<br />
2009:<br />
1. E. Dervishi, Z. Li, Y. Xu, F. Watanabe, V. Saini, A.R. Biris, A.S. Biris,„Horizontally oriented long carbon nanotubes grown on Si substrates by<br />
using a catalytic Chemical Vapor Deposition process‖, ― Nanotech Conference‖, May 3-7, 2009, Houston, TX.<br />
2 T. Mocan, LC Mocan, D. Todea-Iancu , B. Diaconu, S. Simon, D. Lupu , AS. Biris., AR Biris, C Iancu, ―Evaluation of ss-DNA –CNT effects on<br />
HeLa, HEPG2 and PANC-1 cell lines in vitro‖, 36-th International Congress of Physiological Sciences, Kyoto, 2009, Japan (IUPS 2009<br />
3 T Mocan, LC Mocan, S Simon, D Lupu, AS Biris, AR Biris, L Agoston-Coldea, S Clichici, C Iancu, A Muresan, ―Impact of administration dose<br />
and cell line type on the in vitro proliferation effects of ss-DNA CNT‖, 7-th International Stem Cell School on Regenerative Medicine 2-4<br />
Noiembrie 2009, Praga, Republica Ceha. publicata in abstract in volum de rezumate, p 75<br />
4 C.Iancu, LC Mocan, S.Susman, D Rus-Ciuca, O Soritau, T Mocan, S Simon, A Stir, L Agoston-Coldea, AR Biris, S Clichici, A Muresan,<br />
―Effects of ss-DNA-SCNT on stem cell proliferation‖ 7-th International Stem Cell School on Regenerative Medicine 2-4 Noiembrie 2009,<br />
Praga, Republica Ceha. publicata in abstract in volum de rezumate, p 69<br />
2010:<br />
1. Mocan T, Susman S, Rus-Ciuca D., Mihu C, Soritau O, Simon S, Mocan LC, Agoston-Coldea L, Biris AR, Biris AS, Clichici S, Muresan A,<br />
Iancu C, ―Effects of mesenchimal stem cells exposure to single wall carbon nanotubes involve oxidative stress mechanisms―, Joint Meeting of<br />
the Scandinavian and German Physiological Societies, 27-30 martie, 2010, Copenhaga, Danemarca.<br />
2. Mocan T, Iancu C , Clichici S., Mocan L., Susman S., Rus-Ciuca D., Soritau O. , Simon S. , Agoston-Coldea L., Biris AR, Muresan A.,”<br />
Effects of ss-DNA-SWCNT on stem cell proliferation.‖, 8th International Stem Cell School in Regenerative Medicine, 3-5 Septembrie 2010,<br />
Stockholm, Suedia<br />
3. Iorga O., Fustos T., Cozar O., Mocan L., Iancu C.,‖Apoptosis Rate After Selective Thermolysis Of Hepatocarcinoma Cell Lines Treated With<br />
Bovine Serum Albumin Conjugated Carbon Nanotubes‖ International Medical Students' Congress Novi Sad, 15-17 iulie, 2010<br />
4. Fustos T., Iorga O., Mocan L., Iancu C., „Experimental Approach Of Pancreatic Cancer Cell Lines Using Biofunctionalized Single Wall Carbon<br />
Nanotubes‖ ,21 European Students’ Conference, 13-17 octombrie, 2010.<br />
5. Iorga O., Fustos T., Cozar O., Mocan L., Iancu C.,‖Apoptosis Rate After Selective Thermolysis Of Hepatocarcinoma Cell Lines Treated With<br />
Bovine Serum Albumin Conjugated Carbon Nanotubes‖ 21 European Students’ Conference, 13-17 octombrie, 2010<br />
6. Fustos T., Iorga O., Mocan L., Iancu C., „Experimental Approach Of Pancreatic Cancer Cell Lines Using Biofunctionalized Single Wall Carbon<br />
Nanotubes‖ ,International Medical Students' Congress Novi Sad, 15-17 iulie, 2010.
Activitatile prevazute a se realiza in anul 2011:<br />
Aferente etapei IV de evaluare in vivo (pe modele animale<br />
de hepatocarcinom uman), a eficacitatii procedeului de<br />
nanofototermoliza pe baza de nanotuburi de carbon<br />
functionalizate specific cu anticorpi de receptor si<br />
iradiere externa asociata.<br />
Obiectivele ce vor fi atinse:<br />
Generarea unei nanoterapii moleculare cu rol in<br />
tratamentul <strong>hepatocarcinomului</strong>.<br />
Estimarea necesarului de finantare pentru finalizarea<br />
obiectivelor 562000 lei
VA MULTUMESC!