Project financed by European Commission, ERA-NET Co fund, 7th Joint Call – 2016
Translational proof of concept of spintronic micro-nanoparticle non thermal vibrational therapy for glioblastomas – acronym NANOVIBER
Total project costs: 1,201,273 euro
Total requested budget: 811,530 euro
Total INCDMNR UEFISCDI co-financing: 184,750 euro
Poject duration (months): 36
Institut National de la Santé et de la Recherche Médicale (Inserm) Unit1205, Franța, Coordonator
COMMISSARIAT A L’ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES, Franța, Partener
Faculdade de Farmácia da Universidade de Lisboa (FFUL) / iMed.ULisboa, Portugalia, Partener
INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE PENTRU METALE NEFEROASE şi RARE, România, Partener
Responsabil: Dr. Roxana Mioara PITICESCU, tel: 0213522046, fax: 0213522049, email: firstname.lastname@example.org
ARISTOTLE UNIVERSITY OF THESSALONIKI, LTFN LABORATORY, Grecia, Partener
Despite the progress of chemo-‐radiotherapy, molecular and cellular therapies as well as neuro-surgery, glioblastoma remains a deadliness disease. Beside drugs, radiotherapy and surgery, “physical” therapies are synergistic opportunities to solve this major biomedical bottleneck. Paramagnetic parti-cles have been extensively used in association with magnetic stimulation to destroy glioblastoma tissues using thermal strategy. Recently, the impact of vibrational non-‐thermal strategies has been introduced as a new opportunity. In vitro efficacy has been demonstrated by several groups using innovative micro-‐nano-‐particles harboring strong anisotropic magnetic properties. Only one recent publication com-forts the therapeutic efficacy at the preclinical level. To the opposite of the thermal strategy, low cost devices are used to induce vibration providing a strong medico-‐economic transferability of the technology. Grenoble is one of the few international spot working in this field; the group of B. Dieny is internationally recognized in the field of spintronic for electronics. He recently validated the therapeutic interest of specific spintronic particle for anti-‐tumor vibrational therapy in vitro. He also developed an innovative vibrational device for in vitro and in vivo vibrational stimulation using simple magnets rotating at 20 Hz thus generating a local rotating magnetic field.
The objective of this 3 years project is to boost the preclinical validation and toxicology of these particles, to support more rigorously a large translational program. The association of European lea-ders in the field of translational nanomedicine, nano-‐ toxicology, nano-‐regulation, ethics as well as nanofabrication and nano-‐characterization should pave for a proof clinical proof of concept trial opening new medical and industrial perspectives in the nanomedicine area.
STAGE 1/2017 ESTABLISHMENT OF METHODOLOGIES OF CHEMICAL-STRUCTURAL CHARACTERIZATION OF FUNCTIO-NALIZED NANOPARTICS
Period: 01.05.2017 – 20.12.2017
Activity 1.1 Characterization of UV-VIS, FT-IR, SEM and complex thermal analysis of functionalized nanoparticles (P4-IMNR)
Activity 1.2 Characterization of the dispersibility of functionalized nanoparticles (P4-IMNR)
Obiectivul Etapei I a constat în stabilirea metodologiilor de caracterizare chimico-structurală a nanoparticulelor funcționalizate.
The objective of Stage I was to establish the methodologies for chemical-structural characterization of the functionalized nanoparticles.
At this stage they were synthesized by the hydrothermal method at high iron nanoparticle pressures. The nanoparticles thus obtained as well as the samples submitted by the partner P2-CEA / INAC were characterized chemically-structural by the following methods: quantitative chemical analysis, X-ray dif-fraction (DRX), UV-VIS spectrophotometry, FT-IR spectroscopy , optical microscopy (MO), electronic scanning microscopy (SEM) coupled with semicantitative analysis by EDS, complex thermal differential scanning (DSC) thermal analysis and distribution of average particle size by DLS.
Nanoparticles based on iron oxides were synthesized at temperatures of 100-200°C and working pressu-res between 20-1000 bars. It has been found that the synthesis pressure influences the type of crystalli-ne iron oxide phase.
The corroboration of the results obtained in the chemical analysis, DRX, UV-VIS, FT-IR, MO, SEM-EDS and DSC, led to the elaboration of a methodology for chemical-structural characterization of iron oxide nanoparticles. From a dispersibility point of view, a method for characterizing the average particle size in a stable iron oxide suspension in a non-toxic dispersion medium has been developed.
STAGE 2/2018 ESTABLISHMENT OF METHODOLOGIES OF CHEMICAL-STRUCTURAL CHARACTERIZATION OF FUNCTIO-NALIZED NANOPARTICS
Period: 21.12.2017 – 20.12.2018
Activity 2.1 Characterization of thermal stability of functionalized nanoparticles (P4-IMNR)
Activity 2.2 Caracterizarea micro-structurala SEM, TEM, DRX si a proprietatilor magnetice ale nanoparticulelor functionalizate (P4-IMNR)
Obiectivul Etapei II a constat în realizarea metodologiilor de caracterizare chimico-structurală a nanoparticulelor functionalizate.
The objective of Stage II was to carry out methodologies for chemical-structural characterization of functionalised nanoparticles.
At this stage, the chemico-structural characterization methodologies of functionalised nanoparticles were performed by the comparative analysis of commercial magnetotech samples transmitted by P2-CEA / INAC with hydrothermal synthesized magnetite samples in IMNR (P4). Also, samples based on hy-drothermal functionalized iron oxides were analyzed. Thermal stability of nanoparticles of hydrothermal synthesized nanoparticles under various experimental conditions has been demonstrated by performing complex thermal analysis: DSC-TG (including heating and cooling cycles) and DSC. The Curie temperatu-re of the iron oxides obtained (hematite and magnetite) was highlighted. By the chemical-structural characterization of magnetite-based nanoparticles it was found that hydrothermal synthesized powders have crystalline sizes between 17-29 nm; crystallizes in a cubic system in the form of magnetite; form agglomerations of the order of hundreds of nm (when suspended) or aggregates of the micron order (observed by SEM analysis). The sample with the smallest polydispersity index, with the cubic and the best magnetic properties, was synthesized at 200°C and 100 atm. Based on the national and British standards on nanomaterial characterization methods and good laboratory practice on thermal analysis, the DLS method and the TEM / HRTEM microscopy, three characterization methods have been develo-ped: DSC-TG, SEM and DRX..
- M. Cursaru, R. M. Piticescu, A.-M. Mocioiu, D. V. Drăguț, A. G. Plăiașu, C. M. Ducu, „Synthesis and characterization of iron oxide nanoparticles for biomedical applications”, 1st International Conference on Emerging Technologies in Materials Engineering EmergeMAT and 4th International Workshop on Materials under Extreme Conditions SUPERMAT, 14-16.11.2018, Bucharest, Romania (poster)
- M. Piticescu, L. M. Cursaru, A.-M. Mocioiu, D. V. Dragut, A. G. Plaiasu, C. M. Ducu, „The influence of synthesis parameters on iron oxide nanoparticles”, International Workshop on Advances in Nanomaterials, 17-19.09.2018, Magurele, Romania (oral presentation)
- 2 ISI papers in preparation
- Morel, C. Thébault, C. Naud, H. Joisten, S. Leulmi, C. Iss, M. Morcrette, G. Ortiz, Y. Hou-Broutin, T. Livache, R. Calemczuk, M. Carrière, P. Sabon, I. Joumard, S. Auffret, et B. Dieny “Vibrating Magnetic Particles for Cancer Cells Destruction”, Invited oral presentation BIMS 2018 – Bio Inspired Magnetic Systems, Exeter (UK), July 9-12, 2018.
- Morel, C. Naud, H. Joisten, S. Leulmi, C. Iss, M. Morcrette, G. Ortiz, Yanxia Hou-Broutin, T. Livache, R. Calemzuck, M. Carrière, P. Sabon, I. Joumard, S. Auffret, et B. Dieny “Design of Magnetic Nanoparticles for Magneto-mechanical Cancer Cells Destruction”, Poster, MagMeet 2018 – 12th International Conference on the Scientific and Clinical Applications of Magnetic Carriers, Copenhagen (DEN), May 22-26, 2018.
- Thébault, C. Naud, E. Billiet, H. Joisten, M. Carrière, Y. Hou-Broutin, R. Morel, and B. Dieny “Magnetic particle oscillations triggered by a rotating magnetic field for mechanical treatment of glioblastoma”, Poster, Congrès SF-Nano 2018 Société Française de Nanomédecine, Montpellier (FR), December 3-5, 2018.
- Patent: “Procédé de fabrication d’un fluide biocompatible comportant une poudre de particules magnétique, fluide biocompatible comportant une poudre de particules magnétiques”, R. Morel, B. Dieny, et H. Joisten. French Patent n° 1852971 deposited on 04/05/2018.
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