Nanoterapia fototermica selectiva a hepatocarcinomului prin

Coordonator: Universitatea de Medicina si
Farmacie ―Iuliu Hatieganu‖ Cluj-Napoca
Director proiect: Conf. Dr. Iancu Cornel
Catedra Chirurgie 3 Cluj-Napoca

Parteneri în consorţiu:
• P1. Spitalul Clinic de Urgenta Prof. Dr. ―Octavian Fodor‖
Cluj-Napoca
• P2. Institutul Naţional de Cercetare-Dezvoltare pentru
Tehnologii Izotopice şi Moleculare Cluj-Napoca
• P3 Universitatea de Stiinte Agricole si Medicina
Veterinara Cluj Napoca
• P4 Institutul Inimii Nicolae Stancioiu Cluj-Napoca
• P5 Nanotechnology Center at University of Arkansas at
Little Rock, SUA
Buget: 2.000.000 RON
Adresa web: http://clinicachirurgie3.ro/nanohep

Obiectivele specifice caractere de originalitate:
• Identificarea target-urilor membranare specifice in scopul dirijarii
selective a nanotubulilor de carbon la nivelul celulelor maligne
hepatice
• Functionalizarea (legarea) nanotuburilor de carbon cu elemente
complementare (anticorpi) target-urilor neoplazice hepatice
specifice identificate.
• Cercetarea potentialului tumoricid al iradierii LASER in vitro asupra
celulelo hepatice tumorale continand CNT internalizate
• Identificarea modalitatilor practice de administrare a CNT
functionalizate si marcate specific in organismul gazda
Beneficiarii rezultatelor:
• pacientii cu carcinom hepatocelular
• personalul medical
• cercetatori, ingineri,
• studenti
• agenti economici

• Buget de stat: 130000 RON
• Precursori/rezultate intermediare Etapa 1
• Infiintarea Societatii Romane de Nanomedicina
• Infiintarea si dotarea Centrului de Cercetari in Nanomedicina al
UMF Cluj-Napoca si Spitalului Clinic O. Fodor (5 incaperi
insumand 110 m2)
• Cereri de brevet:
• Attorney Docket No. 999084B (07.10.2008) TITLE OF
INVENTION: ―Metallic nanoparticles coated with graphitic shells
as localized radio frequency absorbers for cancer therapy‖
INVENTOR NAMES: Alexandru S. Biris, Yang Xu, Zhongrui Li,
Meena Mahmood, and Alexandru R. Biris (brevet uspto)
• Cererea de brevet cu titlul: ―Procedeu de determinare a
sulfamidelor din muşchi de pasăre prin extracţie dispersivă în
fază solidă folosind nanotuburi de carbon de tip
MWCNT‖.Autori :Bele Constantin, Matea Cristian Tudor, Dan
Lupu, Alexandru Biriş, Iancu Cornel, Mocan Lucian. (brevet
OSIM:125476 A2 din 19.09.2008)

•Precursori/rezultate
intermediare Etapa 1
• Studii de interes national:
• Studiu privind prelevarea, cultivarea si intretinerea celulelor maligne
hepatice
• Studiu privind realizarea xenogrefelor de hepatocarcinom uman la
soarecii imunodeprimati prin implantare de tesuturi tumorale de la
pacienti
• Studiu privind functionalizarea (legarea) nanotuburilor de carbon cu
anticorpi specifici pentru membrana celulelor tumorale hepatice cu rol in
targeting celular
• Studiu privind nanofototermoliza LASER a celulelor maligne marcate cu
anticorpi
• Studiu privind administrarea si testarea in vivo a noilor materiale
nanobiocompozite cu rol antineoplazic
• Prezentari la conferinte internationale (sept 2008-feb 2009): 6
• Stagii de perfectionare in strainatate pentru tineri doctoranzi pe tema
proiectului: 3

Echipamente Cercetare-UMF Cluj
1 Vortex –agitator magnetic
Fact 9202103/
03.10.2008
1799.07
2 Lampa laser Fact 58/ 14.04.2008 21003.50
3 Distilator
Fact 9203323/
19.11.2008
1799.98
4
Aparat sectionare tesuturi cu Fact 0012733/
ultrasunete
30.10.2008
31951.5
5 Ph-metru de laborator
Fact 9202723/
30.10.2008
1798.79
5 Baie de apa termostatata cu accesorii
Fact 9203334/
20.11.2008
14778.24
6 Balanta Kern
Fact 9202722/
30.10.2008
1799.04
Echipamente Cercetare-P1 SCUCN Cluj
7 Centrifuga de racire HETTICH
Fact 9202091/
03.10.2008
15.551,91
8 Masina pt. spalat sticlarie MIELE
Fact 1359/
13.10.2008
15.562,88
9 Microscop model AE-31
Fact 9202709/
30.10.2008
11.715,67

Stagiu de pregatire 07.09.2008-06.10.2008 pentru 3 doctoranzi ai UMF Iuliu Hatieganu la Centrul
de Nanotehnologii al Universitatii Little Rock, SUA,.
4 teme de doctorat in domeniul terapiei tintite molecular a cancerelor utilizand nanotuburi specific
functionalizate:
“Nanoterapia in cancerele digestive- modele experimentale.”-
drd. Mocan Lucian
“Implicatiile stresului oxidativ in relatie cu nanomaterialele”
drd.Mocan Teodora
“Functionalizarea nanotuburilor de carbon cu aplicatii in nanomedicina”
drd. Simon Stefania
“Sinteza nanoparticulelor cu aplicatii in terapia cancerelor”
drd. Matea Cristian
Alti doctoranzi participanti acitiv in proiect: Drd. Iancu Dana, Zaharie Florin, Mihaileanu
Florin
Studenti participanti activ in proiect: Fustos Tiberiu, Iorga Otilia, Cozar Octavian, Hossu
Miana (participanti la 2 conferinte internationale studentesti pe tema proiectului Novi
Sad, Berlin)
Cuantumul salariilor la tinerii sub 35 de ani 67.2% (din totalul bugetului alocat pe salarii)

• Buget de stat: 65000
• Precursori/rezultate intermediare
• Publicatii ISI in extenso in jurnale din strainatate cu factor de impact: 8
• Prezentari la conferinte internationale cu tema proiectului (cu abstracte publicate in jurnale
ISI): 4
• Capitol de carte publicat de o editura internationala: Bele Constantin ( autor) ‖Carbon
Nanotubes as a New Solid Phase Extraction Sorbent for Analysis of Environmental
Pollutants ― , capitol în ― Carbon Nanotubes ― ( editor Vedran Kordic ) , la editura IN-TECH,
Vienna, Austria , ISBN 978-953-7619
• Dotarea Centrului de Cercetari in Nanomedicina
• Investitii in echipamente de cercetare: 17000 RON
1
ECHIPAMENTE CD CO UMF
Hota
microbiologica
Fact
9206408/06.08.2009 17000

• Buget de stat: 262245
• Publicatii ISI in extenso in jurnale din strainatate cu factor de impact: 4
• Publicatii ISI (in press) in extenso in jurnale din strainatate cu factor de impact: 1
• Publicatii ISI (sub review extern) in extenso in jurnale din strainatate cu factor de impact:3
• Prezentari la conferinte internationale cu tema proiectului publicate in abstract: 6
• Capitol de carte publicat de o editura internationala: Cornel Iancu ( author) ‖ Human Cord Blood-Derived Stem Cells in
Transplantation and Regenerative Medicine― , capitol în "Stem Cells", ISBN 978-953-307-232-6., la editura IN-TECH, Vienna,
Austria, in press
Cerere brevet:Cerere de brevet OSIM cu nr. a1157/2010 cu titlul :Procedeu de obţinere a nanotuburilor de carbon de tip MWCNT
funcţionalizate, ultra-scurte prin oxidare controlata.Autori :Matea Cristian Tudor, Bele Constantin, Iancu Cornel, Mocan Lucian, Orza
Anamaria-Ioana
Propunere FP7-Euronanomed 2-nd call, 11 iunie 2010 (Coordonator UMF Cluj-Dr. Iancu Cornel, Parteneri: USAMV Cluj, Ben Gurion
University, Nejev Israel, Ikerlat Polymers, Spania): Selective targeted necrosis of liver cancer using radiofrequency activated bioligand
nanocompounds.
Modele experimentale noi din punct de vedere stiintific:
‣ Model experimental de functionalizare a nanotuburilor de carbon cu albumina serica umana
‣ Model experimental de tratament in vitro al carcinomului hepatocelular prin administrare de nanotuburi de carbon functionalizate cu
albumina serica umana combinate cu iradiere laser externa
•

Lista cu lucrări ştiinţifice publicate in reviste cotate 2009
1. Cornel Iancu, Ioana R. Ilie, Carmen E. Georgescu, Razvan Ilie, Alexandru R. Biris, Teodora Mocan, Lucian C. Mocan,
Florin Zaharie, Dana Todea-Iancu, Sergiu Susman, Dan Rus Ciuca, Alexandru S. Biris. ―Applications of Nanomaterials in Cell
Stem Therapies and the Onset of Nanomedicine‖. Particulate Science and Technology, 2009, 27: 6, 562 — 574
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
N, Galanzha EI, Biris AS, Zharov VP. Synergistic enhancement of cancer therapy using a combination of carbon nanotubes
and anti-tumor drug. Nanomed. 2009 Dec;4(8):883-93 (Impat Factor 6.7)
3. C. Bele, C.T. Matea , M. MorarRomanian Journal of Biochemistry , vol. 46, ISSN 1582-3318, p.118-19 Fuctionalized
single walled nanotubes as a new solid phase microextraction sorbent for analysis of food preservatives
4. C. T. Matea, C. Bele, M. Morar Romanian Journal of Biochemistry , vol. 46, ISSN 1582-3318, p. 120-121 Carbon
nanotubes as solid phase micro-extraction sorbent for the determination of benzene in urine
5. Li Z, Kunets VP, Saini V, Xu Y, Dervishi E, Salamo GJ, Biris AR, Biris AS. Light-harvesting using high density p-type
single wall carbon nanotube/n-type silicon heterojunctions. ACS Nano. 2009 Jun 23;3(6):1407-14. (Impat Factor 7.5)

Publicatii ISI 2009
6. E. Dervishi, Z. Li, Y. Xu, V. Saini, A.R. Biris, D. Lupu, A.S. Biris, „Carbon Nanotubes: Synthesis, Properties, and
Applications‖, Particul. Sci. Technol., 27(2), 107-125, 2009.
7. E. Dervishi, Z. Li, F. Watanabe, Y. Xu, V. Saini, A. R. Biris, A. S. Biris, ―Thermally controlled synthesis of single-wall
carbon nanotubes with selective diameters‖, J. Mater. Chem., 19(19), 3004-30012, 2009.
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,
―The influence of Fe-Co/MgO Catalyst composition on the growth properties of carbon nanotubes‖, Particul. Sci.
Technol., 27(3), 222-237, 2009.
9. Dervishi E, Li Z, Watanabe F, Biswas A, Xu Y, Biris AR, Saini V, Biris AS. Large-scale graphene production by RFcCVD
method. Chem Commun (Camb). 2009 Jul 21;(27):4061-3.
10.

Publicatii ISI cu factor de impact 2010
1. Xu Y, Mahmood M, Fejleh A, Li Z, Watanabe F, Trigwell S, Little RB, Kunets VP, Dervishi E, Biris AR, Salamo
GJ, Biris AS. Carbon-covered magnetic nanomaterials and their application for the thermolysis of cancer cells.
Int J Nanomedicine. 2010 Apr 7;5:167-76. (IF:3)
2. Mahmood M, Casciano DA, Mocan T, Iancu C, Xu Y, Mocan L, Iancu DT, Dervishi E, Li Z, Abdalmuhsen M,
Biris AR, Ali N, Howard P, Biris AS. Cytotoxicity and biological effects of functional nanomaterials delivered to
various cell lines. J Appl Toxicol. 2010 Jan;30(1):74-83. (IF:2.2)
3. Yang Xu, Alokita Karmakar, Daoyuan Wang, Meena W. Mahmood, Fumiya Watanabe, Yongbin Zhang, Ashley
Fejleh, Phillip Fejleh, Zhongrui Li, Ganesh Kannarpady, Syed Ali, Alexandru R. Biris, Alexandru S. Biris
Multifunctional Fe3O4 Cored Magnetic-Quantum Dot Fluorescent Nanocomposites for RF Nanohyperthermia
of Cancer Cells The Journal of Physical Chemistry C 2010 114 (11), 5020-5026 (IF:3.6)
4. Alexandru Radu Biris, Enkeleda Dervishi, Stefania Simon, Dan Lupu, Ioan Misan, Cornel Iancu, Simona Valeria
Clichici, Yang Xu, Fumia Watanabe, Alexandru Sorin Biris, Analytic studies of high quality singlewall carbon
nanotubes synthesized on a novel Fe:Mo:MgO catalyst, Physica E: Low-dimensional Systems and
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
1. Iancu C, Mocan L, Bele C, Orza A, Tabaran F., Catoi C, Stiufiuc R, Stir A, Matea C, Iancu D, Agoston-Coldea
L, Zaharie F, Mocan T., Carbon nanotube-enhanced laser thermal ablation for the destruction of liver cancer cells in
vitro by specific delivery of multi-walled carbon nanotubes (MWCNT) functionalized with human serum
albumin (HSA), Int J Nanomed. In Press. (IF=2.8)
2. “Ex vivo photothermal ablation of human pancreatic cancer with albumin functionalized multi-walled carbon nanotubes.”,
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
submitted to ACS Nano IF: 7.5 (sub review extern, Manuscript ID: nn-2010-020538)
3. Simon, Stefania; Rada Ilie, Ioana; Dervishi, Enkeleda; Xu, Yang; Biris, Alexandru; Biris, Alexandru; Mocan, Teodora;
Mocan, Lucian; Todea Iancu, Dana; Iancu, Cornel; Misan, Ioan; Lupu, Dan; Li, Zhongrui; Biswas, Abhijit"Studies on Near
Infrared Optical Absorption, Raman Scattering and Corresponding Thermal Properties of Single- And Double-Walled Carbon
Nanotubes for Possible Cancer Targeting and Laser-Based Ablation“ submitted to The Journal of Physical Chemistry
(IF:2.7),(sub review extern- Manuscript ID: jp-2010-10110u)
4. Mocan L, Agoston L, Bele C, Stiufiuc R, Mocan T, Iancu C "Genotoxicity of nanomaterials with applications in cancer
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
2008
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.
Lupu, ―Multifunctional Coating with Carbon Nanotubes for Electrostatic Mitigation and Their Formation by Laser Heating‖, IEEE
Annual Meeting, Industrial Aplication Society, Edmonton, Canada, October 2008.
2. A. Biris, T. Mocan “Cytotoxicity of Carbon Nanomaterials: Single-Wall Nanotube, Multi-Wall Nanotube‖, CANCER
TARGETING BY NANOMATERIALS, MIAMI, FLORIDA, 25-29 SEPTEMBRIE, 2008
3. A. Biris, D.Todea-Iancu, ―Interactions of Nanomaterials with Biological Systems‖, CANCER TARGETING BY NANOMATERIALS,
MIAMI, FLORIDA, 25-29 SEPTEMBRIE, 2008
4. D.Todea-Iancu, ―Optimal nanomaterial administration methods for human cancer treatment‖, CANCER TARGETING BY
NANOMATERIALS, MIAMI, FLORIDA, 25-29 SEPTEMBRIE, 2008
5. T. Mocan , ―Selectivity optimization of nanotargeting the pancreatic cancer cells‖, CANCER TARGETING BY NANOMATERIALS,
MIAMI, FLORIDA, 25-29 SEPTEMBRIE, 2008
6. L.Mocan, A. Biris ―Nanotherapy in pancreatic cancer, experimental models‖, CANCER TARGETING BY NANOMATERIALS,
MIAMI, FLORIDA, 25-29 SEPTEMBRIE, 2008

• Prezentari la congrese internationale:( publicatii in abstract in reviste indexate ISI)
2009:
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
using a catalytic Chemical Vapor Deposition process‖, ― Nanotech Conference‖, May 3-7, 2009, Houston, TX.
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
HeLa, HEPG2 and PANC-1 cell lines in vitro‖, 36-th International Congress of Physiological Sciences, Kyoto, 2009, Japan (IUPS 2009
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
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
Noiembrie 2009, Praga, Republica Ceha. publicata in abstract in volum de rezumate, p 75
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,
―Effects of ss-DNA-SCNT on stem cell proliferation‖ 7-th International Stem Cell School on Regenerative Medicine 2-4 Noiembrie 2009,
Praga, Republica Ceha. publicata in abstract in volum de rezumate, p 69
2010:
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,
Iancu C, ―Effects of mesenchimal stem cells exposure to single wall carbon nanotubes involve oxidative stress mechanisms―, Joint Meeting of
the Scandinavian and German Physiological Societies, 27-30 martie, 2010, Copenhaga, Danemarca.
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.,”
Effects of ss-DNA-SWCNT on stem cell proliferation.‖, 8th International Stem Cell School in Regenerative Medicine, 3-5 Septembrie 2010,
Stockholm, Suedia
3. Iorga O., Fustos T., Cozar O., Mocan L., Iancu C.,‖Apoptosis Rate After Selective Thermolysis Of Hepatocarcinoma Cell Lines Treated With
Bovine Serum Albumin Conjugated Carbon Nanotubes‖ International Medical Students' Congress Novi Sad, 15-17 iulie, 2010
4. Fustos T., Iorga O., Mocan L., Iancu C., „Experimental Approach Of Pancreatic Cancer Cell Lines Using Biofunctionalized Single Wall Carbon
Nanotubes‖ ,21 European Students’ Conference, 13-17 octombrie, 2010.
5. Iorga O., Fustos T., Cozar O., Mocan L., Iancu C.,‖Apoptosis Rate After Selective Thermolysis Of Hepatocarcinoma Cell Lines Treated With
Bovine Serum Albumin Conjugated Carbon Nanotubes‖ 21 European Students’ Conference, 13-17 octombrie, 2010
6. Fustos T., Iorga O., Mocan L., Iancu C., „Experimental Approach Of Pancreatic Cancer Cell Lines Using Biofunctionalized Single Wall Carbon
Nanotubes‖ ,International Medical Students' Congress Novi Sad, 15-17 iulie, 2010.

Activitatile prevazute a se realiza in anul 2011:
Aferente etapei IV de evaluare in vivo (pe modele animale
de hepatocarcinom uman), a eficacitatii procedeului de
nanofototermoliza pe baza de nanotuburi de carbon
functionalizate specific cu anticorpi de receptor si
iradiere externa asociata.
Obiectivele ce vor fi atinse:
Generarea unei nanoterapii moleculare cu rol in
tratamentul hepatocarcinomului.
Estimarea necesarului de finantare pentru finalizarea
obiectivelor 562000 lei

VA MULTUMESC!