Objectives:

1. MAPLE synthesis of Graphene Oxide (GO), signaling path inhibitors and epigenetic modulators (BRAFi, and HDACi), GO/BRAFi, GO/HDACi thin films.

2. Advanced physical-chemical characterizations of the MAPLE composite coatings.

3. Synthesis of compositional libraries thin films of GO/BRAFi/HDACi by C-MAPLE.

4. Biodegradation tests on samples and evaluation of inhibitors release.

5. Tailoring cellular responses by coatings with variable composition.

6. Results dissemination.

Expected results:

1. Protocol for GO, BRAFi, HDACi, GO/BRAFi, GO/HDACi thin films synthesis that preserves the properties of starting materials and are adherent to different substrates;

2. Protocol for laser evaporation process and thin films growth for tailoring coatings properties. Identification of the optimum deposition conditions for C-MAPLE experiments;

3. C-MAPLE protocol for the fabrication of complex compositional libraries of nanocomposite films;

4. Protocol for tuning active substances release kinetics from the composite coatings;

5. Identification of optimum inhibitors dosage and surface properties with respect to cells behavior. Construction of the compositional diagram and identification of the optimum combination index, able to modulate synergistic effects that could direct cell apoptosis;

6. Scientific and financial reports. ISI papers published in international journals and participation (oral and poster presentation) at national and international conferences.

Paper published in ISI journals:

 1. “Matrix-Assisted Pulsed Laser Evaporation: A novel approach to design mesoporous carbon films” Carbon 122 (2017) 484-495 - *IF(2016) = 6.337 Emanuel Axente, Mihai Sopronyi, Camélia Matei Ghimbeu, Cristina Nita, Aissam Airoudj, Gautier Schrodj and Felix Sima

2. „Combinatorial laser synthesis of compositional library thin films for screening of molecular-targeted agents in melanoma”

To be submitted to ACS Combinatorial Science (2017) - *IF(2016) = 3.168

L.E. Sima,* I. Negut, V. Grumezescu, S. Iosub, G. Chiritoiu, C. Hapenciuc, F. Sima, and E. Axente,*

3. „Functionalized graphene oxide nanomaterials: in vitro cytotoxicity and BRAF inhibition in melanoma cells”

FEBS JOURNAL   Volume: 284   Special Issue: SI   Supplement: 1   Pages: 328-328   Meeting Abstract: P.5.2-018   Published: SEP 2017

V. Grumezescu, I. Negut, S. Iosub, G. Chiritoiu, C. Hapenciuc, F. Sima, L.E. Sima,* and E. Axente,*

4. „Compositional analysis of drugs by laser-induced breakdown spectroscopy”

Journal of Applied Spectroscopy, Vol. 84, No.3, (2017) - *IF(2016) = 0.572

S.A. Beldjilali, E. Axente, A. Belasri, T. Baba-Hamed, and J. Hermann

5. “Ideal radiation source for plasma spectroscopy generated by laser ablation”

Physical Review E, 96, 053210 (2017) - *IF(2016) = 2.366

Jörg Hermann, David Grojo, Emanuel Axente, Christoph Gerhard, Milos Burger, Valentin Craciun

6. „New bio-active, antimicrobial and adherent coatings of nanostructured Carbon double-reinforced with Silver and Silicon by Matrix-Assisted Pulsed Laser Evaporation for medical applications”

Under Review - Applied Surface Science (Ref: APSUSC-D-17-10875) 2017, - *IF(2016) = 3.387 L. Duta, C. Ristoscu, G.E. Stan, M.A. Husanu, C. Besleaga, M.C. Chifiriuc, V. Lazar, C. Bleotu, F. Miculescu, N. Mihailescu, E. Axente, D. Bociaga, M. Badiceanu, Ion N. Mihailescu

7. “Gradient coatings of strontium hydroxyapatite/ zinc β-tricalcium phosphate as a tool to modulate osteoblast/osteoclast response”Under Review - Journal of Inorganic Biochemistry (2018) - *IF(2016) = 3.348 Elisa Boanini, Paola Torricelli, Felix Sima, Emanuel Axente, Milena Fini, Ion N. Mihailescu, Adriana Bigi

Book chapter:

1 “Recent Advances of Graphene Family Nanomaterials for Nanomedicine”

Chapter, in “Fullerens, Graphenes and Nanotubes: A Pharmaceutical Approach” 1st Edition, Eds. Alexandru Grumezescu, Elsevier, ISBN 9780128136911 (2018).

Irina NEGUT, Valentina GRUMEZESCU, Livia SIMA* and Emanuel AXENTE*

 2. “Combinatorial laser synthesis of biomaterial thin films: selection and processing for medical applications”

Chapter, in “Advances in the Application of Lasers in Materials Science”, Eds. M. Dinescu. D.B. Geohegan, A. Miotello and P.M. Ossi, Springer (2018). Emanuel Axente, Carmen Ristoscu, Adriana Bigi, Felix Sima, and Ion N. Mihailescu

3. “Nanoparticle generation by double pulse laser ablation”

Chapter 9, in “Pulsed Laser Ablation: Advances and Applications in Nanoparticles and Nanostructuring Thin Films”, Eds. I.N. Mihailescu and A.P. Caricato, Pan Stanford Publishing Pte Ltd., Singapore (2017) ISBN 9781315185231. Emanuel Axente, Tatiana E. Itina and Jörg Hermann

4. “Biopolymer thin films synthesized by advanced pulsed laser techniques”

Chapter 4, in "Recent Advances in Biopolymers", Ed. F. Parveen, InTech ISBN 978-953-51-4613-1, 2016.

Emanuel AXENTE, Felix SIMA, Carmen RISTOSCU, Natalia MIHAILESCU, Ion N. MIHAILESCU

5. “Bioresponsive surfaces and interfaces fabricated by innovative laser approaches”

Chapter 12, in “Advanced Materials Interfaces” (eds A. Tiwari, H. K. Patra and X. Wang), John Wiley & Sons, Inc., Hoboken, NJ, USA. doi: 10.1002/9781119242604.ch12, ISBN 9781119242451, 2016.

F. Sima, E. Axente, C. Ristoscu, O. Gallet, K. Anselme, I.N. Mihailescu

National and International Conferences:

 1. “Porous carbon thin films by Matrix-Assisted Pulsed Laser Evaporation from environmental friendly organic precursors”

Poster presented at Symposium X : New frontiers in laser interaction: from hard coatings to smart materials of the E-MRS 2017 Spring Meeting, May 22-26, 2017, Strasbourg (France). E. Axente, M. Sopronyi, C.M. Ghimbeu, F. Sima

2. “MAPLE synthesis of Graphene Oxide composites for nanomedicine”

Poster presented at IONS Balvanyos Conference 2017, International OSA Network of Students, 25-28 July 2017.

I. Negut, V. Grumezescu, S. Iosub, C. Hapenciuc, F. Sima, G. Chiritoiu, L.E. Sima* and E. Axente*

3. „Functionalized graphene oxide nanomaterials: in vitro cytotoxicity and BRAF inhibition in melanoma cells”

Conference: 42nd Congress of the Federation-of-European-Biochemical-Societies (FEBS) on From Molecules to Cells and Back Location: Jerusalem, ISRAEL Date: SEP 10-14, 2017V. Grumezescu, I. Negut, S. Iosub, G. Chiritoiu, C. Hapenciuc, F. Sima, L.E. Sima,* and E. Axente,*

4. P103 - “Functionalized Graphene Oxide nanoscale thin films for melanoma therapy”

10th International Conference on Photoexcited Processes and Applications, August 29 – September 2, 2016, Brasov, RomaniaI. Negut, V. Grumezescu, C. Hapenciuc, T. Alexandru, F. Sima, L.E. Sima,* and E. Axente,*

5. P-07.01.3-030 “On the in vitro cytotoxicity of graphene oxide nanomaterials”

The FEBS Journal 283 (Suppl. 1) (2016) 129–417 DOI: 10.1111/febs.13808 V. Grumezescu, I. Negut, F. Sima, E. Axente, L. E. Sima

6. “Combinatorial Matrix Assisted Pulsed Laser Evaporation: thin films deposition with gradient from two biocompatible materials”

INERA Conference 2016, Vapor Phase Technologies for Metal Oxide and Carbon Nanostructures, 5-9 July, 2016, Velingrad, Bulgaria M. Sopronyi, F. Sima, E. Axente, I. Mihailescu

7. P.6.2. - "MAPLE fabricated graphene oxide thin films as tunable platforms for cancer therapy" The 5th International Colloquium “Physics of Materials” (PM 5), 10-11 November 2016,  Bucharest, Romania

I. Negut, V. Grumezescu, C. Hapenciuc, S. Iosub, F. Sima,  L.E. Sima, E. Axente