TumoR microEnvIronment Normalization FOR enhanCed photodynamic thErapy

H2020 HORIZON-MSCA-2023-PF-01-01 “TumoR microEnvIronment Normalization FOR enhanCed photodynamic thErapy” (HORIZON-MSCA-2023-PF-01-01, 101152646, “REINFORCE”)

Abstract

The progression of cancer is closely associated with alterations in the mechano-cellular phenotype and in the structure and mechanical properties of the tumor microenvironment (TME) in a complex and not well-understood manner. Desmoplasia, a tumour-associated fibrotic reaction, is responsible for tumor stiffening, poses a major barrier to effective drug delivery. Although novel therapeutic strategies that target cancer cells are emerging, their efficacy varies due to intra- and inter-patient variability as well as tumor heterogeneity. Notably, photodynamic therapy (PDT) is gaining prominence as a compelling alternative. This two-stage treatment harnesses both light energy and a specialized drug (photosensitizer, PS) to target cancer cells upon activation by a specific wavelength of light. However, the effectiveness of PDT is greatly compromised by various resistance factors originating from the complex TME. These factors can present several biological barriers, including desmoplasia. In this project, we propose the use of TME normalization treatment with approved anti-fibrotic drugs in combination with PDT. We aim to test the hypothesis that the combination of anti-fibrotic drugs that remodel and normalize the TME with PDT can increase the PDT efficiency. The specific research objectives are focused on breast cancer (BC) and includes in vitro study of the effect of different components of PDT treatment on BC cells, in vivo study of the effectiveness of the combination of PDT with anti-fibrotic treatment in murine BC models and mathematic modelling to optimize the combination therapies. In the proposed project, the fellow will acquire scientific and complementary skills according to his personalized career development plan and through advanced training, international and inter-sectoral mobility will reach a position of professional maturity in research.

The fellow : Stylianos Vasileios Kontomaris

ORCID ID: https://orcid.org/0000-0003-4843-1208

Scopus ID: https://www.scopus.com/authid/detail.uri?authorId=55569403600

Google Scholar: https://scholar.google.com/citations?user=BL5a1E0AAAAJ&hl=en

Contact: s.kontomaris@research.euc.ac.cy

Biography

Dr. Stylianos Vasileios Kontomaris received a degree in Physics in 2008 from the University of Patras (Greece) and a Master of Science in Microsystems and Nanodevices in 2010 from the National Technical University of Athens (N.T.U.A.). Moreover, he received his Ph.D. in the area of Biophysics, Biomedical Engineering and Nanotechnology (February 2016) from the National Technical University of Athens (School of Electrical and Computer Engineering, Biomedical Optics & Applied Biophysics Laboratory). He is the author of more than 58 peer reviewed journal papers in a wide range of scientific fields, including, biomedical engineering, nanotechnology, and physics (h – index 15, Google Scholar). In addition, he is the author of 6 research papers in Conference Proceedings and he has also been invited in more than 12 national and international conferences to present research activities in the field of Nanotechnology and Biomedical Engineering. He has worked as a Lecturer in Greek Fire Service Academy (2017) and as a research associate at the Biomedical Simulations and Imaging (BIOSIM) Laboratory of the School of Electrical and Computer Engineering (N.T.U.A.) (2018 -2019). Since September of 2016, he is also a Senior Lecturer in Athens Metropolitan College (A.M.C.) (Faculty of Engineering and Architecture). In addition, since September of 2021 he is also the Program Leader of the Electrical and Electronic Engineering Course of Athens Metropolitan College. Since July of 2021, he is the C.E.O. of BioNanoTec LTD. He has worked in several research projects. In particular, he participated in the project entitled ‘Development, installation, and management of a network for measuring non-ionizing radiation from mobile telephony’ (funded by the Institute of Communication and Computer Systems (ICCS) of N.T.U.A.), and in the project entitled ‘Provision of recording and control services for the publication of the results of electromagnetic radiation’ (also funded by the Institute of Communication and Computer Systems (ICCS) of N.T.U.A). In addition, he is the coordinator of the project 3D NANOBIOSAMPLES /CONCEPT/0521/0069 (3D Characterisation Of The Nanomechanical Properties Of Biological Samples) funded by the Cyprus Research and Innovation Foundation. In July 2024, he joined European University Cyprus (School of Sciences) as a Marie Skłodowska-Curie Postdoctoral Fellow (project ‘REINFORCE: Tumor Microenvironment Normalization for Enhanced Photodynamic Therapy’).

Presentation

Dr. Kontomaris presented the project during the Spring 2024 Info Day of Cancer Mechanobiology and Applied Biophysics Group

Publications

Paper 1 of the project: Kontomaris, S.V.; Malamou, A.; Stylianou, A. Accurate Modelling of AFM Force-Indentation Curves with Blunted Indenters at Small Indentation Depths. Micromachines 2024, 15, 1209. https://doi.org/10.3390/mi15101209

Paper 2 of the project: Kontomaris, S.V.; Malamou, A.; Stylianou, A. A new method for AFM mechanical characterization of heterogeneous samples with finite thickness. Journal of Mechanics 2024, 40, 552-564. https://doi.org/10.1093/jom/ufae047

Paper 3 of the project: Kontomaris, S.V.; Malamou, A.; Stylianou, A.,Simplifying Data Processing in AFM Nanoindentation Experiments on Thin Samples, Eng, 2024, 6(2), 32, https://www.mdpi.com/2673-4117/6/2/32

Paper 4 of the project: Kontomaris, S.V.; I. Psychogios, Malamou, A.; Stylianou, A., Monitoring the Distance and Velocity of Protons in a Medium for Biomedical Applications Using a Straightforward Mathematical Approach,

Sci 2025, 7(2), 49; https://doi.org/10.3390/sci7020049

Paper 5 of the project: I. Psychogios, Kontomaris, S.V., Malamou, A.; Stylianou, A., A Novel Approach to Calculate the Range of High-Energy Charged Particles Within a Medium, Atoms, 2025, 13 (5), https://doi.org/10.3390/atoms13050038

Paper 6 of the project: Kontomaris, S.V.; Malamou, A.; Stylianou, A. The Young’s Modulus as a Mechanical Biomarker in AFM Experiments: A Tool for Cancer Diagnosis and Treatment Monitoring. Sensors 2025, 25, 3510. https://doi.org/10.3390/s25113510

Paper 7 of the project: Kontomaris, S.V.; Psychogios, I.; Stergiopoulos, M.; Malamou, A.; Stylianou, A. Quantitative Criteria for the Validity of the Elastic Half-Space Assumption in AFM Nanoindentation. Next Materials 2025, 9, 101180. https://doi.org/10.1016/j.nxmate.2025.101180

Paper 8 of the project: Kontomaris, S.V.; Malamou, A.; Ismail, G.M.; Psychogios, I.; Stylianou, A. Global linear modeling of AFM indentation curves for soft samples with various indenter geometries. Next Materials 2025, 9, 101299. https://doi.org/10.1016/j.nxmate.2025.101299

Paper 9 of the project: Kontomaris, S.V.; Malamou, A.; Ismail, G.M.; Katsiki, A.; Stylianou, A. Beyond Hertz: Accurate Analytical Force–Indentation Equations for AFM Nanoindentation with Spherical Tips. Metrology 2025, 5, 63. https://doi.org/10.3390/metrology5040063

Paper 10 of the project: Kontomaris, S.V.; Ismail, G.M.; Malamou, A.; Stylianou, A. Mechanical Nonlinear Oscillations Using a Hertzian-Type Restoring Force. Vibration 2025, 8, 74. https://doi.org/10.3390/vibration8040074

Paper 11 of the project: Kontomaris, S.V.; Psychogios, I.; Malamou, A.; Stylianopoulos, T.; Stylianou, A. Mathematical modeling of tumor nanomechanical fingerprints: A weighted skew-normal distribution approach for cancer diagnosis and treatment monitoring. Next Nanotechnology 2026, 9, 100365. https://doi.org/10.1016/j.nxnano.2026.100365

Paper 12 of the project: Kontomaris, S.V.; Malamou, A.; Psychogios, I.; Stylianou, A. A Practical Approach for Determining Depth-Dependent Mechanical Properties of Soft Materials in AFM Indentation via Polynomial Fitting and a New Model for Cellular Mechanics. Eng 2026, 7, 75. https://doi.org/10.3390/eng7020075

Paper 13 of the project: Kontomaris, S.V.; Pettermeridi, M.; Malamou, A.; Stylianou, A. Nonlinear Modeling and Perturbation Analysis of Cell Population Dynamics under External Factors: A Pilot Study of Low-Level Red Laser Irradiation on Lung Cancer Cells. Journal of Interdisciplinary Research Applied to Medicine 2026; accepted on 16 May 2026.

Conferences

Kontomaris, S.V.; Stylianou, A. Simplifying the Fitting Procedure in AFM Indentation Experiments on Samples with Finite Thickness. In Proceedings of the 9th Annual International Conference on Mechanical Engineering, Annual Academic Meetings of the Engineering Division of the Athens Institute, Athens, Greece, 2025; Oral presentation.

Kontomaris, S.V.; Stylianou, A. Overcoming challenges in the AFM mechanical nanocharacterization of soft heterogeneous biological materials. AFM BioMed Conference 2025, Barcelona, Spain, 8–11 April 2025; Oral presentation.