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Dep. ANALIZE, TESTE, INCERCARI

Metode inovative de fotochemoterapie cu noi fotosensibilizatori nanostructurati de la sinteza la studiu clinic
Spectrometrie de
fluorescenta de raze X

Cromatografie de
lichide de inalta precizie
 
VIASAN    

DESPRE PROIECT
  • Denumire program Cercetare de excelenta CEEX
  • Denumire modul 4-Sanatate (Viasan)
  • Denumire domeniu prioritar Sanatate
  • Denumire proiect METODE INOVATIVE DE FOTOCHEMOTERAPIE CU NOI FOTOSENSIBILIZATORI NANOSTRUCTURATI – DE LA SINTEZA LA STUDIU CLINIC
  • Director proiect Prof.Dr.chim.Rodica-Mariana Ion
  • Date contact (tel., fax, e-mail) 021.316.30.94/021.312.34.93/analize@icechim.ro
  • Denumire UCD INSTITUTUL NATIONAL DE CERCETARE DEZVOLTARE PENTRU CHIMIE SI PETROCHIMIE - ICECHIM - BUCURESTI

REZUMAT
Proiectul METODE INOVATIVE DE FOTOCHEMOTERAPIE CU NOI FOTOSENSIBILIZATORI NANOSTRUCTURATI – DE LA SINTEZA LA STUDIU CLINIC si-a propus implementarea procedurii de terapie fotodinamica in patologia dermatologica umana, prin stabilirea unei retele formata din institutii de cercetare, universitati din diverse regiuni ale tarii si din unitati spitalicesti, care detin experienta stiintifica si practica necesara.
Obiectivele studiului propus au vizat:
  • 1.Sinteza unei game de compusi cu proprietati fotosensibile din clasa porfirinelor si ftalocianinelor ale caror proprietati fotofizice si fotochimice vor fi identificate - obiectiv care a condus la caracterizarea completa a substantelor obtinute si la selectia primara a unei game de compusi care intrunesc criteriile de puritate si eficienta necesare in aplicatia bio-medicala.
  • 2.Conditionarea compusilor caracterizati in vehicole ca hidrogelurile sau obtinerea lor in structuri supramoleculare pe suport de nanoparticule – obiectiv care a condus la obtinerea unei game de compusi cu o fotostabilitate ridicata, utilizabili in dermatologie
  • 3.Studii complexe de toxicologie in vitro pe linii celulare utilizate standard in domeniu (linia celulara P388 si L1210), linii de fibroblaste (linia 1184), keratinocite (linia DOK), melanom uman (FM3), celule endoteliale normale umane (HUVEC-C) – obiectiv ce a condus atat la stabilirea criteriilor secundare de selectie a compusilor fotosensibili si a tipului de vehicole, cat si la determinarea eficientei lor asupra unor linii celulare cu relevanta in dermatologie.
  • 4.Studii complexe de toxicologie in vivo pe modele animale de carcinogeneza la nivelul pielii si pe modele animale cu tumori murine transplantabile (melanom B16, carcinom Lewis) in etapele de initiere, promotie si progresie tumorala – obiectiv ce a creat premizele trecerii la studiul clinic de faza I, prin selectia tertiara a compusului/compusilor fotosensibili si a vehicolului cel mai eficient in paractica dermatologica
  • 5.Studii clinice de faza 1 pe pacienti diagnosticati in cele doua unitati spitalicesti cu profil dermatologic implicate in proiect si pentru care s-a obtinut consimtamantul informat scris si acordul Comisiilor de Etica din unitatile respective si a Colegiului Medicilor – obiectivul a tintit testarea in patologia dermatologica umana compusilor fotosensibilizanti, urmarind atat parametrii clinici ai pacientului, cat si monitorizarea parametriilor imuni ai acestora (citotoxicitatea NK)
Pe tot parcursul proiectului s-au derulat in paralel studii de cercetare fundamentala ce au vizat investigarea cailor de inducere a proceselor apoptotice, tintele moleculare ale terapiei fotodinamice experimentale si utilizarea celulelor stem dermale incarcate cu compusii testati, in vederea cresterii eficientei TFD experimentale. Astfel, proiectul a initiat pentru prima data in tara o retea de unitati de cercetare si clinice, care are scop implementarea terapiei fotodinamice in patologia dermatologica umana


PARTENERI
    Consortiul acestui proiect este urmatorul:
  • 1. INCDCP-ICECHIM, Bucuresti, Director Proiect Prof.Dr.Rodica-Mariana Ion
  • 2. INCD-Victor Babes, Bucuresti, Responsabil proiect: Dr.Monica Neagu
  • 3. UMF Carol Davilla, Responsabil Proiect Sef Lucrari dr. Daniela Baconi
  • 4. Universitatea Valahia Targoviste, Responsabil Proiect Sef Lucrari Dr.Dragos Brezoi
  • 5. Universitatea Transilvania Brasov, Responsabil Proiect Prof.Dr.Silvia Patachia
  • 6. Spitalul Colentina, Responsabil Proiect, Asist.Dr.Daniel Boda
  • 7. Spitalul Stefan Longhin, Responsabil Proiect Conf.Dr.Mihai Alecu

CRITERII
    CRITERII DE ELIGIBILITATE
  • proiectul este finalizat sau in curs de finalizare la nivelul anului 2008 Proiectul se finalizeaza in septembrie 2008
  • proiectul este prezentat pe pagina Web (adresa): www.vbabes.ro; www.old.icechim.ro;


    • CRITERII DE EVALUARE
  • 1. gradul de complexitate si noutate ale proiectului
    • Proiectul a initiat pentru prima data in tara o retea de unitati de cercetare si clinice, care are scop implementarea terapiei fotodinamice in patologia dermatologica umana.

    Gradul de noutate al proiectului propus s-au concretizat in:
    • realizarea fluxului sinteza-testare clinica a unui nou produs medicamentos cu activitate antineoplazica
    • aplicarea terapiei fotodinamice in patologia dermatologica, la nivel national
    • nanostructurarea compusilor fotosensibilizanti si aplicarea lor in studii in vitro si in vivo.
    • realizarea procedurilor de incarcare a fotosensibilizatorilor in celule stem in model animal cu scopul cresterii eficientei TFD experimentale

    Gradul de complexitate al proiectului rezida in:
    • reunirea catorva colective multidisciplinare de cercetatori (chimisti, fizicieni, biochimisti, imunologi, medici) care vor realiza pentru prima data pe plan national fundamentarea la nivel clinic a unei terapii fotodinamice antitumorale utilizand produse autohtone. Rezultatele proiectului privind o terapie aflata in stadiu avansat pe plan international de testare clinica si paraclinica vor fi diseminate la reuniuni si publicate in reviste de specialitate, oferind clinicilor din tara o informare si un ghid privind o terapie la standarde internationale. Datorita atragerii in colectivul care propune proiectul a unor tineri doctoranzi implicati in studiul in acest domeniu, rezultatele preconizate s-au materializat si in specializarea acestor tineri intr-un domeniu de varf si realizarea a 4 teze de doctorat in cele trei universitati din tara.
    • metodologia prezentata in cadrul proiectului cuprinde tehnici de biologie celulara, moleculara si de chimie fizica la standarde internationale
    • crearea premizelor stiintifice si metodologice pentru introducerea in tara noastra a unei modalitati terapeutice in patologia dermatologica.

  • 2. gradul de protectie a rezultatelor obtinute in cadrul proiectului
    • In curs de brevetare: Cerere brevet A 00489/25.06.2008
    Titlu: UTILIZAREA PORFIRINEI TETRASULFONATE IN FABRICAREA UNUI AGENT FOTOSENSIBILIZATOR PENTRU TERAPIA DERMATOLOGICA
    Inventatori: Ion Rodica-Mariana, INCDCP-ICECHIM, Bucuresti
    Neagu Teodora Monica, INCD�Victor Babes, Bucuresti
    Constantin Carolina, INCD�Victor Babes, Bucuresti
    Boda Daniel, Spitalul Clinic Colentina, Bucuresti

  • 3. gradul de competitivitate a rezultatelor obtinute in cadrul proiectului
    • Beneficii directe
    • obtinerea unor noi substante biologic active/medicamente
    • realizarea pentru prima data pe plan national a unui studiu clinic de faza 1 pentru aplicarea terapiei fotodinamice in domeniul dermatologic
    • initierea documentatiei privind trecerea la studiul clinic de faza 2
    • rezultate brevetabile: din proiect a rezultat o cerere de brevet depusa la OSIM A00489/25.06.2008
    Beneficii indirecte
    • Metodele prezentate in cadrul proiectului se gasesc la standarde internationale, iar rezultatele obtinute in cadrul proiectului creaza premizele intrarii colectivelor de cercetare in retele de excelenta europeana (COST D39) care are ca obiectiv prioritar investigarea medicamentelor inovative in domeniul cancerului.
    • Colectivele de cercetare implicate cuprind chimisti, biologi, biochimisti, imunologi, medici, colective care, pana la propunerea acestui proiect, au desfasurat activitati de cercetare in domeniu. In acest context, s-a creat un colectiv multidisciplinar, sub forma unei retele �deschise� implicate in studiul terapiei fotodinamice.
    S-au desfasurat o serie de actiuni suport constand in principal intr-un plan de difuzare, diseminare si promovare in mediile stiintific si economic a rezultatelor obtinute, precum:
    • organizarea de work-shopuri (etapele IV si VI ale planului de realizare) (anexata este materialul prezentat la Workshop-ul din 2007)
    • prezentarea cunostintelor acumulate prin proiect in cursurile studentilor, avand in vedere angrenarea a trei universitati, si/ sau introducerea unor noi capitole in cursurile universitare de profil
    • prelegeri la cursuri post-universitare (lista anexata)
    • realizarea unor teze de doctorat cu subiecte in domeniu la nivelul celor trei universitati implicate
      • 1. Carolina Constantin, INCD Victor Babes, teza sustinuta in 2007
      • 2. Stegan Varga, Universitatea Transilvania, Brasov, teza ce va fi sustinuta in 2009;
      • 3. Dragos Brezoi, Universitatea Valahia, Targoviste, teza sustinuta in 2007
      • 4. Radu Claudiu Fierascu, INCDCP-ICECHIM, Bucuresti, teza ce va sustinuta in 2010
    • prezentarea rezultatelor prin lucrari publicate in reviste de specialitate si comunicate in cadrul unor simpozioane nationale/internationale (etapele III, IV, V), conform listelor de lucrari anexate
    • consultanta tehnica de specialitate
    Mentiune: Prezentul proiect nu a mai fost finantat din alte surse bugetare sau extrabugetare

  • 4. gradul de viabilitate a proiectului
    • Una dintre problemele majore cu care se confrunta lumea medicala, este cancerul. Cancerul este considerat ca fiind a doua cauza importanta a mortalitatii pe intregul glob. In Romania, in ultima decada, s-au inregistrat schimbari majore in structura morbiditatii si mortalitatii populatiei. S-a inregistrat o crestere rapida a numarului tumorilor maligne, acestea reprezentand a doua cauza de deces, imediat dupa afectiunile cardiovasculare. Puternicul impact al cancerului asupra societatii romanesti se regaseste nu numai in numarul mare al deceselor (circa 38 000 pe an, ceea ce reprezinta 13-14% din total) ci si in numarul noilor cazuri inregistrate (circa 45 000 pe an) si al bolnavilor in viata (circa 200 000). Pornind de la aceste date, tratarea cancerului a devenit una dintre prioritatile nationale din domeniul medical.
    Avand in vedere toate aceste aspecte, diseminarea la Congrese si alte manifestari stiintifice internationale de profil a rezultatelor si cunostintelor acumulate pe parcursul anilor privind sinteza porfirinelor si utilizarea lor in domeniul terapiei cancerului a fost de o importanta majora, si au fost realizate atat de conducatorul cat si de membrii acestui consortiu. Ca rezultat al activitatilor anterioare, consortiul organizat pentru acest proiect, detine prioritati la scara industriala in domeniul macrociclurilor terapeutice.
    Prin acest proiect de cercetare s-a urmarit realizarea de noi sisteme cu caracteristici spectrale de absorbtie in regiunea IR apropiat, la care sa se investigheze proprietatile fotofizice si fotochimice, studiile propuse a se realiza aduc relevanta pentru procesele de agregare si/sau transfer de energie prin prisma interactiilor fotosensibilizatori /substrat viu. Posibilitatile de succes ale proiectului pot fi asigurate printr-o buna coordonare a grupelor de cercetare in domeniu. Proiectul propus are in vedere demonstrarea viabilitatii acestei metode de tratare a cancerului si alinierea cercetarii de pe plan national cu cercetarea internationala in domeniu.
    Viabilitatea si sansele de succes ale proiectului au avut la baza experienta membrilor echipei, conceptia proiectului, si cooperarea internationala initiata deja. Astfel, proiectul este viabil datorita urmatoarelor considerente:
    1. Experienta si rezultatele obtinute de INCDCP-ICECHIM in domeniul sintezei porfirinelor/ftalocianinelor, cu aplicatii in terapia fotodinamica a cancerului
    2. Experienta si rezultatele obtinute de partenerii ICECHIM si INCD Victor Babes in domeniul studiilor de toxicologie in vitro/in vivo in domeniul terapiei fotodinamice
    3. Experienta si rezultatele obtinute de Spitalul Colentina si Spitalul Stefan Longhin in domeniul studiilor clinice interne si internationale, dintre care unele realizate chiar in domeniul terapiei fotodinamice
    4. Modul de conceptie si de management performant ale proiectului
    5. Colaborarea initiata deja intre colectivele partenerilor implicati.
    6. Cooperarea internationala initiata deja de membrii echipelor de cercetare (vezi anexele)
    7. Aparatura moderna detinuta de partenerii implicati in proiect si metodologia de inalt nivel utilizata (anexa)
    8. Planificarea judicioasa a termenelor, activitatilor si colectivelor angrenate
    9. Nucleul complex realizat pe plan national de specialisti in domeniul terapiei fotodinamice, care, prin activitatile desfasurate in cadrul acestui program, a crescut vizibilitatea stiintifica in plan european

  • 5. gradul de vizibilitate a rezultatelor obtinute in cadrul proiectului
    • 5.1. Carti publicate
    • 1. R.M.Ion-Fotochimie. Principii si Aplicatii. Editura FMR, Bucuresti, Vol.1, 2005 ISBN 973-8151-40-6 ISBN Vol 1: 973-8151-41-4
    • 2. R.M.Ion-Fotochimie. Principii si Aplicatii. Editura FMR, Bucuresti, Vol.2, 2006 ISBN (10): 973-8151-40-6 ISBN (10) Vol 2: 973-8151-42-2 ISBN (13): 978-8151-42-0
    • 3. R.M.Ion-Fotochimie. Principii si Aplicatii. Editura FMR, Bucuresti, Vol.3, 2006 ISBN (10) 973-8151-40-6 Vol 3-2006- Bibliogr.- ISBN (10): 973-8151-43-0 ISBN (13): 978-973-8151-43-7
    • 4. R.M.Ion-Fotochimie. Principii si Aplicatii. Editura FMR, Bucuresti, Vol.4, 2007 ISBN 973-8151-40-6 Vol 4-2007- Bibliogr.- ISBN: 978-973-8151-44-4

    5.2. Lucrari publicate in jurnale ISI
    • 1. E.Stoykova, E. , Sabotinov, O., Ion, R.M., Alexandrova, R, Reliability of the survival dose estimated from in vitro cytotoxicity testing in photodynamic therapy, Biotechnology and Biotechnological Equipment, Vol. 22 (2), 2008, pp. 754-758
    • 2. RM Ion, D.Boda, Supramolecular nanotubes porphyrin-based generated by aggregation process, Rev.Chim., 59(2) 2008, pp.205-207;
    • 3. S.Apostol, RM Ion, L.Tugulea, Spectral methods for nitrogen deficiency evaluations in maize plants, JOAM, 10(6) 1478-1481(2008);
    • 4. A.Hanyz, RM Ion, D.Wrobel., A.Nuta, Spectral characterization of selected stilbenztriazine dyes-structural cis-trans, isomerisation, J.Molec.Str., in press, 2008;
    • 5. MG Van der Horst, GA van Albada, RM Ion, I.Mutikainen, U.Turpeinen, S.Tanase, J.Reedijk, extended networks generated from the interaction of rare-earth(III) ions and pyridine 2-carboxamide base ligands, Eur.J.Inorg.chem., 2008(13), 2170-2176(2008);
    • 6. RM Ion, D.V.Brezoi, A study on the photodynamic therapy of photosensitizer-coated magnetic nanoparticles, J.Optoel.Adv. Mat. 9(4)936-939(2007);
    • 7. RM Ion, D.V.Brezoi, M.Neagu, G.Manda, C.Constantin, Laser effect in photodynamic therapy of tumors, Proc.SPIE, 6606, 66061G-660671G (2007);
    • 8. RM Ion, M.A Calin, Comparative study of some nano and microsensitizers in photodynamic inactivation of microorganisms, J.Optoel.Adv. Mat. 9(4)1933-1938(2007);
    • 9. S.Patachia, R.Ion, St.Varga, Porphyrin encapsulation in nanostructured hydrogels, J.Optoel.Adv. Mat. 9(4)1814-1820(2007);
    • 10. M.Neagu, G.Manda, C.Constantin, E.Radu, RM Ion, Synthetic porphyrins in experimental photodynamic therapy induce a different antitumoral effect, J.Porphyrins and Phthalocyanines, 12(01) 58-65(2007);
    • 11. E.Stoykova, K.Nedkova, O.Sabotoniv, RM Ion, R.Alexandrova, In vitro cytotoxicity assessment of second generation PS for PDT, J.Optoel.Adv. Mat. 9(2)490-493(2007);
    • 12. RM Ion, Patricia del V.Repossi, Gerardo Arguello, Porphyrin-tyrosine conjugate as synergic photosensitizer in photodynamic therapy, Rev.Chimie (Bucharest), 52(11), 2007;
    • 13. RM Ion, Photodynamic therapy: a photochemical concept for cancer therapy, Rev.Roum.Chim., 12, 2007
    • 14. E.Stoykova, K.Petrova, RM Ion, K.Nedkova, D.Wrobel, A.Dudkowiak, Monte Carlo study of optical dosimetry in a photodynamic treatment of tumors with different PS, Comptes Rendue Bulgarian Acad.Sci., 2007;
    • 15. S.Patachia, S.Varga, RM Ion, Development of controlled release devices for PDT, Pollack Periodica, 2(2) 131-140 (2007);
    • 16. RM Ion, M. Neagu, G. Manda, C. Constantin, E. Radu, M.Calin, Mechanisms in photodynamic therapy, Photosensitizers and cellular localization on K562 cells, SPIE Proc., 6632, 6632Q, 2007;
    • 17. A.Siejak, D.Wrobel, RM Ion, Study of resonance effects in cobalt phthalocyanines, J.Photochem.Photobiol., A:Chem., 2006, 181 (2-3) pp.180-187;
    • 18. RM Ion, Photodynamic therapy: a new concept and a clinical reality for medicine, Acta Bio-optica et Informatica Medica, 1, 2006, pp.37-49;
    • 19. RM Ion, Photodynamic therapy as a new method for laser-assisted sensitization of cancer cells, Proc. Symp. Photonics Technologies for 7th Framework Programm, pp.312-315, 2006;
    • 20. DV Brezoi, RM Ion, Temperature treatment and composition effect on properties of functionalized nanopowders FexOy-PPy for biomedical applications, Proc. Symp. Photonics Technologies for 7th Framework Programm, pp.542-545, 2006;
    • 21. RM Ion, MA Ionita, B.Carstocea, Photochemical degradation of Rb used as drug into photodynamic therapy, Rev Chimie, Bucharest, 57(7), 718-721(2006);
    • 22. RM Ion, DV Brezoi, I.Udrea, Sisteme supramoleculare gazda-musafir cu aplicatii biomedicale, Rev Chimie, 57(8), pp. 886-889(2006);
    • 23. RM Ion, DV Brezoi, Nanocomposite based on PPy with porphyrin-?-oxo-dimers, Nanotrends,2(1),pp.1-11, 2006;

    5.3. Lucrari publicate in jurnale CNCSIS
    • 1. RM Ion, Photodynamic therapy and the oxidative stress for cellular organelles, Physiology, 18(2), 58(2008), pp.37-38;
    • 2. S.Clichici, M.Perde-Schrepler, A.Filip, D.Daicoviciu, P.virag, E.Fischer-Fodor, I.Brie, RM Ion, C.Login, A.Muresan, in vitro and in vivo assessment of the efficiency of photodynamic therapy with TSPP, Physiology, 18(2), 58(2008), pp.17-18;
    • 3. R.Cosgarea, S.Senila, I.Baldea, M.Susan, S.Dreve, RM Ion, Study of phototoxic effects of ALA and TSPP on primary human keratinocytes and carcinoma cell cultures. The evaluation of cytotoxic and phototoxic effects of chitosan on cell cultures, Physiology, 18(2), 58(2008), pp. 19;
    • 4. RM Ion, DV Brezoi, S.Patachia, St.Varga, Z.Cristu, M.Mateescu, Noi tendinte in domeniul nanomaterialelor pentru medicina, Proc.ses St. UVT, 33-41, 2007;
    • 5. S.Patachia, S.Varga, RM Ion, Nanostructured PVA hydrogels materials as vehicles for encapsulation and controlled release of porphyrin-based cancer therapeutics, Bull Univ.Transilvania, Brasov, 4, 153-160, 2007;
    • 6. VIR Niculescu, RM Ion, C.Mardare, Image processing 2D delta approximation, Rom.J.Physics, 51(5-6) 663-666(2006);
    • 7. VIR Niculescu, RM Ion, C.Stancu, M.Leonovici, The post-gaussian wavelets, Analele Universitatii de Vest, Timisoara, Vol.XLVI, 2005, Seria Fizica;
    • 8. RM Ion, Nanomaterials:from materials science to chemical science, Metalurgia International, 6/2006, 33-40, 2006;

    5.4. CARTI SAU CONTRIBUTII IN CARTI CU COTATIE ISBN
    • 1. RM Ion,RC Fierascu, I.Dumitriu, Multifunctional porphyrinic materials encapsulated into macronets with photochemotherapeutic applications, Proc.Burgas
    • 2. RM Ion, Mathematical model for isosbestic points of porphyrins. Implications in cryotherapy and photodynamic therapy, Proc. 9th WSEAS International Conference on MATHEMATICS & COMPUTERS IN BIOLOGY & CHEMISTRY (MCBC '08) Bucharest, pp.82, 2008;
    • 3. RM Ion, L.Maresca, D.Migoni, FP Fanizzi, Concept of associated PDT with porphyrin-CisPt drug system and applications of HeLa cells, IEE Computer Society, Proc.Biotechno, International Conference on Biocomputation, Bioinformatics, and Biomedical Technologies , 2008, pp.70-75,
    • 4. S.Varga, S.Patachia, RM Ion, Analysis of mass transfer of encapsulated porphyrins from PVA-based hydrogel an eperimental study, Proc 5 th WSEAS International Conference on heat and mass transfer, ISBN: 978-960-6766-31-2, pp.231-236, 2008
    • 5. DV Brezoi, RM Ion, Temperature treatment and composition effect on properties of functionalized nanopowders FexOy-PPy for biomedical applications, Book of abstract, OPERA 2015, pp.223, 2006;
    • 6. RM Ion, Photodynamic therapy as a new method for laser-assisted sensitization of cancer cells, Book of abstract, OPERA 2015, pp.125, 2006;

    5.5. Simpozioane, conferinte, congrese tara
    • 1. RM Ion, Photonic metallic nanostructures in photodynamic therapy, The 4th edition of the International Conference "Advanced Topics in Optoelectronics, Microelectronics and Nanotechnologies, Cta, 2008
    • 2. RM Ion, R.C.Fierascu, I.Dumitriu, Advanced new materials with applications, The 4th edition of the International Conference "Advanced Topics in Optoelectronics, Microelectronics and Nanotechnologies, Cta, 2008
    • 3. RM Ion, S.Dreve, Supramolecular Assemblies of Functional Nanoporphyrins in Therapeutics, Complexity and Intelligence of the Artificial and Natural Complex Systems. Medical Applications of the Complex Systems. Biomedical Computing, Tg-Mures, 2008
    • 4. RM Ion, G.Cocina, TPPS4 nanotubes architecture for nanorobots with application in cerebral aneurysm, Bio-Inspired Computational Methods Used for Difficult Problems Solving. Development of Intelligent and Complex Systems, BICS, Tg.Mures, 2008
    • 5. RM Ion, Photodynamic therapy and the oxidative stress for cellular organelles, Al 10-lea Congres al Societatii Romane de Stiinte Fiziologice, Cluj, 2008
    • 6. S.Clichici, M.Perde-Schrepler, A.Filip, D.Daicoviciu, P.Virag, E.Fischer-Fodor, I.Brie, RM Ion, C.Login, A.Muresaan, in vitro and in vivo assessment of the efficiency of photodynsmic thereapy with TSPP, Al 10-lea Congres al Societatii Romane de Stiinte Fiziologice, Cluj, 2008
    • 7. R.Cosgarea, S.Senila, I.Baldea, M.Susan, S.Dreve, RM Ion, Study of phototoxic effects of ALA and TSPP on primary human keratinocytes and carcinoma cell cultures. the evaluation of cytotoxic and phototoxic effects of chitosan on cell cultures, Al 10-lea Congres al Societatii Romane de Stiinte Fiziologice, Cluj, 2008
    • 8. RM Ion, I.Dumitriu, RC Fierascu, Implications and effects of nanotechnologies in medical researrch, Agigea, 2008
    • 9. RM Ion, L.Maresca, D.Migoni, FP Fanizzi, Concept of associated PDT with porphyrin-CisPt drug system and applications of HeLa cells, International Conference on Biocomputation, Bioinformatics, and Biomedical Technologies , 2008, Bucharest;
    • 10. RM Ion, S.Dreve, DV Brezoi, Chitosan-based biomaterials for laser / sensitizer assisted immunotherapy, TEHNOMUS, 2007;
    • 11. RM Ion, S.Dreve, S.Pop, TSPP-chitosan blends. Preparation and physical properties, BIOMMEDD’06, Cluj, 2007
    • 12. S.Dreve, E.Indrea, D.Silipas, RM Ion, R.Cosgarea, A.Filip, M.Perde-Schreppler, I.Brie, Chitosan-based hydrogels with porphyrins for PDT, PIM, Cluj, 2007
    • 13. S.Dreve, E.Indrea, D.Silipas, RM Ion, R.Cosgarea, A.Filip, M.Perde-Schreppler, I.Brie, Bioactivity of new chitosan formulations for PDT, PIM, Cluj, 2007;
    • 14. S. Patachia, S. VargA, R. Ion, Nanostructured poly (vinylalcohol) hydrogel materials as vehicles for the encapsulation and controlled release of porphyrin-based cancer therapeutics, BRAMAT, Brasov, 2007
    • 15. RM Ion, I.Dumitriu, RC Fierascu, Organized supramolecular materials base don porphyrins, BRAMAT, Brasov, 2007
    • 16. RM Ion, Photodynamic therapy: a photochemical concept for cancer therapy, ROMPHYSCHEM , Bucharest, septembrie 2006;
    • 17. RM Ion, DV Brezoi, M.Neagu, G.Manda, C.Constantin, Laser effect in photodynamic therapy of tumors, ALT 2006, Brasov, septembrie 2006;
    • 18. S.Patachia, R.Ion, S.Varga, Photodegradation kinetics of porphyrins used in PDT, ROMPHYSCHEM, Bucuresti, sept., 2006;
    • 19. S.Patachia, RM Ion, M.Rinja, A.Papancea, M.Voinea, E.Samoila, C.Baciu, S.Varga, Hidrogeluri nanostructurate pe baza de PVA cu utilizari in medicina, farmacie, protectia mediului si senzoristica, Seminar National de Nanostiinte si Nanotehnologie, Martie, Bucuresti, 2006;
    • 20. S.Patachia, C.Baciu-Florea S.Varga, RM Ion, Electrolytes influence pn PVA hydrogels used for pharmaceutical application, ROCAM 2006, Bucharest;
    • 21. S.Patachia, RM Ion, S.Varga, M.Rinja, Porphyrin encapsulation in nanostructured hydrogels, ROCAM, Buharest, sept, 2006;
    • 22. RM Ion, DV Brezoi, A study on the photodynamic therapy of photosensitizer-coated magnetic nanoparticles, IBWAP, Constanta, iulie, 2006;
    • 23. Z.Bacinschi, F.Oprea, RM Ion, Al2O3-Cr Cermets, MATEHN’06, Cluj, 2006;
    • 24. S.Patachia, St.Varga, R.Ion, Influenta caracteristicilor morfologice ale hidrogelurilor sensibile la stimuli pe baza de PVA, asupra proprietatilor de eliberare controlata, Simp.ICCF-Cercetarea medicamentului intre informatie si stiintele vietii, Bucuresti, 2006;
    • 25. RM Ion, S.Dreve, C.Gadea, Nanomaterials through molecular self-assembly for nanomedicine, BIOMMEDD’06, Iasi, 2006
    • 26. M.Neagu, G.Manda, C.Constantin, RM Ion, Efectul porfirinelor de sinteza asupra celulelor immune normale, Book of Abstract, Simp.ICECHIM, 2006, pp.94;
    • 27. RM Ion, MA Calin, M.Neagu, G.Manda, C.Constantin, E.Radu, Image analysis in PDT, Book of Abstract, Simp.ICECHIM, 2006, pp.93;
    • 28. St.Varga, S.Patachia, RM Ion, The application of PVA based hydrogels for the decontamination of porphyrins-containing medical wastewaters, EnvEdu, Brasov, 2006;
    • 29. St.Varga, S.Patachia, RM Ion, Matrix-encapsulated drug interactions in sustained release devices based on PVA hydrogels; a case tudy for porphyrins used in cancer therapy, Zilele Academiei Iesene, 2006;

    5.6. Simpozioane, conferinte, congrese strainatate
    • 1. RM Ion, I. Dumitriu, RC Fierascu, Implications and effects of nanotechnologies in medical research, 4th international conference on oxidative stress in skin medicine and biology 11 - 14 september 2008, Andros, Greece
    • 2. RM Ion, Nanoparticles in photodynamic therapy-mediated oxidative stress. Romanian experience in drug carriers and clinical applications, 4th international conference on oxidative stress in skin medicine and biology 11 - 14 september 2008, Andros, Greece
    • 3. RM Ion, RC Fierascu, I. Dumitriu, G.Cocina, Carbon nanotubes architecture as photodynamic nanorobots with application in cerebral aneurysm, 4th international conference on oxidative stress in skin medicine and biology 11 - 14 september 2008, Andros, Greece
    • 4. RM Ion, M.A.Calin, Novel nanostructured materials based on porphyrin/c60 photosensitizers for local cancer treatment, IUPAC 2008, Goteborg, 2008
    • 5. RM Ion, D.V. Brezoi, E. Chirtop, Synthesis of CoFe2O4 ferrite nanopowder by low-temperature method, Proc. NN'08, Salonic, pp.226;
    • 6. RM Ion, I.Dumitriu, RC Fierascu, ML Ion, VIR Niculescu, Nanomaterials for resatuartion and conservation of romanian Gospel,
    • 7. RM Ion, I.Dumitriuu, RC Fierascu, S.Dreve, New drug nanoicarriers consisting of chitosan pva and cyclodextrine derivatives,
    • 8. A.Ionescu, PV Notingher, S.Cotescu, L.Avadanei, M.Bunea, C.Predut, H.Iovu, RM Ion, Composite materials, fire proofed by using halogen free adituves, MmdE, 2008; ROMSC-20078, Bucharest
    • 9. RM Ion, I.Dumitriu, RC Fierascu, Utilisation of chemical actiniometry to deternine adsorption speed of light in photooxidation chemical reactors, UPG symp
    • 10. RC Fierascu, MA Contineanu, I.Dumitriu, RM Ion, ESR study on radicalic species on the irradiation of aspartic acid,
    • 11. RC Fierascu, I.Dumitriu, ML Ion, A.Catangiu, RM Ion, Modern analytical methods applied in archaeometallurgy coin analysis,
    • 12. I.Dumitriu, RM Ion, RC Fierascu, D. Mates, V. Constantinescu, D.I. Bardac, Chromium biomonitoring in human tumoral tissues, 4th international conference on oxidative stress in skin medicine and biology 11 - 14 september 2008, Andros, Greece
    • 13. RM Ion, RC Fierascu, I.Dumitriu, Multifunctional porphyrinic materials encapsulated into macronets with photochemotherapeutic applications, Burgas
    • 14. RM Ion, ML Ion, RC Fierascu, I.Dumitriu, st. Cosulet, VIR Niculescu, Modern analyticalb methods for historical glass artefacts analysis,
    • 15. S.Patachia, S.Varga, RM Ion, Nanostructured PVA-bsed hybrid materials encapsulating porphyrins from engineering the gelation process to device design for preclinical applications, 4th Int.Symp. Nanostructured and functoional polymer-based materials and nanocomposite, NANOFORUM, Roma, 2008
    • 16. C. Constantin, M. Neagu, G.Manda, I.Neagoe, M. Gherghiceanu, C. Stavaru, RM Ion, Fullerenes-Porphyrin compound as anti-tumoral agents in photodynamic therapy experimental model, ICPP-5, Moscow, 2008
    • 17. C. Constantin, M. Neagu, G.Manda, I.Neagoe, M. Gherghiceanu, C. Stavaru, RM Ion, approaches of fullerene derivatives as antitumoral compounds on K562 cell line, FEBS Greece, 2008
    • 18. RM Ion, Mathematical model for isosbestic points of porphyrins. Implications in cryotherapy and photodynamic therapy, WSEAS, Bucharest
    • 19. RM Ion, L.Maresca, D.Migoni, FP fanizzi, Concept of associated PDT with porphyrin-CisPt drug system and applications of HeLa cells, Biotechno, 2008;
    • 20. S.Varga, S.Patachia, RM Ion, Analysis of mass transfer of encapsulated porphyrins from PVA-based hydrogel an eperimental study, 5th WSEAS International Conference on heat and mass transfer,
    • 30. D.V. Brezoi, R.M. Ion, Synthesis and Characterization of Nanocrystalline Iron Oxides for Nanocomposites with Biomedical Applications, E-MRS, Warsovia, 2007
    • 31. M. Neagu, RM Ion, G. Manda, C. Constantin, I. Neagoe, Z. Cristu, Experimental photodynamic therapy with calix[8] and calix[6]arenes in K562 tumor cell line, IPA Congress, Shanghai, 2007;
    • 32. M. Neagu, G. Manda, C. Constantin, G.Savi, RM Ion, PDT-associated immuno respond in melanoma animal model, IMUNO 2007, Rio de Janeiro, Brazil;
    • 33. RM Ion, M. Neagu, G. Manda, C. Constantin, E. Radu, M.Calin, Mechanisms in photodynamic therapy, Photosensitizers and cellular localization on K562 cells, ECBO, Munchen, 2007;
    • 34. S.Dreve, A.Muresan, A.Filip, D.Daicoviciu, S.Clichici, M.Perde-Schreppler, RM Ion, E.Indrea, D.Silipas, Cytotoxic effects of chitosan-based formulations “in vitro� and “in vivo� experiments, NANOFORUM , Duesseldorf, 2007;
    • 35. S.Dreve, RM Ion, A.Filip, M.Perde-Schreppler, E.Indrea, I.Bratu, C.Ratiu, Chitosan-based nanoparticles for medical applications, Applications of chitosan in Medical Sciences, Venetia, Italia, 2007;
    • 36. RM Ion, Spectral properties of dyes-potential sensitizers in photodynamic therapy, ICP 200, Koln, Germany;
    • 37. S.Clichici, A.Filip, A.Muresan, S.Suciu, D.Daicoviciu, C.Tatomir, C.Login, A.Joanta, RM Ion, The dynamics of MMPs and reactive oxygen species in experimental Walker tumor, RDPA 2007, Italia.
    • 38. B.Laskowska, B.Barszacz, A.Boguchi, A.Graja, R.Ion, Spectral investigations of fullerene porphyrin complexes and adducts, 7th Biennal Workshop Fullerenes and atomic clusters, St.Petersburgh, Rusia, 2007;
    • 39. RM Ion, RC Fierascu, I.Dumitriu, MA Calin, New synergic photosensitizers in photodynamic therapy, 2nd European Conf. Chemistry for Life Science, Wroclaw, 2007;
    • 40. RM Ion, Photodynamic therapy for cancer treatment current status and COST D20 advances, COST D20 Final Meeting, Brno,Czech Republic, june, 2006
    • 41. RM Ion, Photodynamic therapy as a new method for laser-assisted sensitization of cancer cells, OPERA 2015, Wroclaw, Poland, september, 2006;
    • 42. M.Neagu, G.Manda, C.Constantin, RM Ion, The effect of antineoplastic photodynamic therapy with porphyrins on the functionality of normal immune cells, 1st Joint Meeting of european National Societies of Immunology 6-9 sept, 2006;
    • 43. M.Neagu, G.Manda, C.Constantin, RM Ion, Structural differences of porphyrins in photodynamic therapy induce ditinct antineoplastic effects, Conf.Porphyrins and Phthalocyanines, Roma, July, 2006;
    • 44. G.Manda, M.Neagu, C.Constantin, RM Ion, Tritium-labeled uridine incorporation in nrmal and tumor cells in expeimental photodynamic therapy with synthetic porphyrins, Conf.Porphyrins and Phthalocyanines, Roma, july, 2006;
    • 45. E.Stoykova, K.Nedkoa, O.Sabotinov, RM Ion, R.Alexandrova, In vitro cytotoxicity assessment of second generation photosensitizers for photodynamic therapy, 14th International School Condensed Matter Physics, Varna, september, 2006;
    • 46. S.Patachia, RM Ion, S.Varga, C.Baciu-Florea, E.Samoila, PVA hyrogels as matrix from drug delivery systems, 4th Int.Conf. Polymer Modification, Degradation, and Stabilization, MoDest, San Sebastian, Spain, septembrie 2006;
    • 47. DV Brezoi, RM Ion, Temperature treatment and composition effect on properties of functionalized nanopowders FexOy-PPy for biomedical applications, OPERA 2015, Wroclaw, septembrie, 2006;
    • 48. RM Ion, Photodynamic therapy as a new method for laser-assisted sensitization of cancer cells, OPERA 2015, 2006;
    • 49. RM Ion, Recent development at the interface netween nanomaterials and medicine, ESF-Nanomedicine Symp., Barcelona, Spain, 2006;
    • 50. RM Ion, Natural and synthetic sensitizer-drugs for PDT in dermatology, PHOTODERM 2006, Dusseldorf, 2006

    5.7. Lectii, cursuri invitate in tara si strainatate
    • 1. RM Ion, Photodynamic therapy: sensitizers, mechanism, and clinical applications, GRG, Queen’s College, Oxford, iulie 2006
    • 2. RM Ion, Recent developments at the iterace between nanomaterials and medicine, NANOMEDICINE, Barcelona, september, Spain, 2006
    • 3. RM Ion, Terapia fotodinamica – de la cercetarea de laborator la aplicatiile clinice, ITIM Cluj Napoca, martie 2006
    • 4. RM Ion, Chemical and Clinical aspects of PDT, Humboldt University, 4 december, 2006;
    • 5. RM Ion, Pierre &Marie Curie Universite, Paris, France

    5.8. Premii obtinute la manifestari stiintifice nationale si internationale
    Premiul pentru cea mai buna lucrare prezentata: RM Ion, L.Maresca, D.Migoni, FP Fanizzi, Concept of associated PDT with porphyrin-CisPt drug system and applications of HeLa cells, International Conference on Biocomputation, Bioinformatics, and Biomedical Technologies , 2008, Bucharest;

  • 6. impactul tehnico-economic si social estimat la implementarea proiectului
    • Din punct de vedere economic, terapia fotodinamica a cancerului are avantaje certe vizavi de costul, efcicienta, siguranta si durata terapiei cu citostatice, comparativ cu efectele secundare nedorite ale radioterapiei. In plus, TFD poate veni in completarea actului chirurgical prin localizarea tumorii sau prin interventia la nivelul tumorilor inoperabile sau inabordabile. Terapia fotodinamica se afla in etapele preclinice sau in faze avansate de testare clinica pe plan international si acest proiect creaza o baza de date pentru aplicarea cu costuri reduse in clinicile nationalea unei terapii actuale.

    Impact direct
    Rezultatele proiectului vor oferi clinicianului date care permit:
    • trecerea in fazele de testare clinica 2, 3 si 4 pe un numar crescut de pacienti si patologii dermatologice
    • imbunatatirea terapiei antitumorale si respectiv a starii de sanatate a populatiei active si varstnice
    • eficientizarea terapiei conduce si la un impact economic direct, reducand costurile terapiei clasice antitumorale
    • perspectiva de dezvoltare in continuare a substantelor fotosensibilizante utilizate in TFD a cancerului
    • extinderea utilizarii substantelor fotosensibilizante in fotodiagnoza, avand in vedere ca substantele se incarca preponderent in celulele tumorale, comparativ cu cele normale
    • elaborarea si realizarea unei metode care sa asigure imbunatatirea tratamentelor individualizate, asigurandu-se cresterea procentului de rezultate pozitive in tratarea unor forme de cancer

    Impact indirect
    Impactul asupra mediului stiintific prin:
    • crearea unui model experimental aplicabil in testarea diferitelor clase de compusi fotosensibilizanti
    • formarea unui nucleu de cercetare aplicativa prin colaborarea stiintifica complexa la nivel regional si national
    • posibilitatea intrarii intr-o retea internationala de excelenta in domeniul terapiei fotodinamice, datorita tehnicilor si problemelor stiintifice de mare actualitate abordate
    • cresterea vizibilitatii cercetarii romanesti si accelerarea procesului de aliniere la reglementarilor Uniunii Europene

    Impactul economic se concretizeaza prin :
    • realizarea unor noi substante medicamentoase pentru terapia cancerului;
    • realizarea unei noi metode de tratare a cancerului;
    • deschiderea unor noi oportunitati de tratament alternativ, care implica producerea de lasere performante, sinteza, in tara noastra, a unor structuri porfirinice cu caracteristici impuse, uniforme, ajustabile care sa conduca la procese biocatalitice de foarte inalta selectivitate;
    • realizarea unor economii la bugetul asigurarilor de sanatate prin diminuarea costurilor de tratament si a perioadei de spitalizare, precum si prin diminuarea eforturilor valutare privind importul de medicamente.

    Impactul social se concretizeaza prin:
    • efecte benefice asupra sanatatii populatiei, prin realizarea unei terapii anti-neoplazice neinvazive, cu efecte secundare minime, realizabila ambulator si cu specificitate mai ridicata in comparatie cu chemo si radioterapia
    • recuperare rapida dupa terapie, datorita efectelor secundare minime

    Impactul asupra mediului se concretizeaza prin
    • metodele de terapie bazate pe fotosensibilizare indusa nu sunt toxice comparativ cu radioterapia si chimioterapia
    • sistemele laser utilizate in cadrul proiectului nu presupun in timpul functionarii sau dupa expirarea duratei de viata a acestora emisia sau crearea de substante poluante si periculase pentru mediu.

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