Laser Irradiated Phenothiazines - Application in Breast Cancer Treatment

Project code:
PN-III-P1-1.1-PD-2021-0225
Project number:
PD 25/2021
Funding bodies:
MCID, CNCS - UEFISCDI
Programme:
Postdoctoral Research Project
Coordinator:
National Institute for Laser, Plasma and Radiation Physics (INFLPR)
Project Leader:
Dr. Ana-Maria Udrea
Start date:
01.04.2022
End date:
31.03.2024
Summary

Cancer is responsible for one out of every six fatalities worldwide and is set to become the leading cause of mortality by 2020.

Chemotherapy, radiation, surgery, and a combination of the three are the most common breast cancer therapies. The quality of life in cancer treatment is diminished due to significant side effects and chemotherapy-related toxicities. Multiple drug-resistant breast cancers necessitate the development of novel, more effective, and faster-acting treatments with fewer adverse effects. Genetic profiling of malignant tumours may assist in the creation of individualized therapies. Cancer research requires specific treatment procedures as well as data mining. This project will be a step forward toward narrowing the cancer research gap in the computer-assisted identification of molecules with anticancer characteristics that are generated as photoproducts by the laser irradiation of medicine.

Using in silico techniques and laser radiation, this research will offer a novel approach for repositioning phenothiazines. In this project, we will (i) use molecular docking to anticipate the biological activity of phenothiazines with cancer-targeted receptors; (ii) describe physicochemically the phenothiazine derivative cocktails before and after laser irradiation at various times; and (iii) evaluate the non-irradiated and laser-irradiated phenothiazines in vitro.

Expected results

1. Finding the phenothiazine derivative that inhibits the MCF7 breast cancer cell line using molecular docking.

2. Laser irradiation of the previously identified compound and evaluation of the time stability of the mixture formed by the irradiated phenothiazine and the generated photoproducts.

3. Identifying the most effective therapy to deal with the MCF7 cell line (dose, irradiated or non-irradiated phenothiazine, irradiation time, etc.).

Project Team
Project Leader:
Dr. Ana-Maria Udrea
Mentor:
Dr. Mihail-Lucian Pascu
Outreach of the project

Stage Reports

2022

Stage 1: In silico prediction between phenothiazines and the receptors targeted in breast cancer

Objectives

Computer-aided discovery of the best phenothiazine derivative that will inhibit the breast cancer cell line MCF7.

Deliverables

*Communication to a national or international conference.

*At least 1 article in the yellow zone or above.

*Computational models and databases of the biological activities of the phenothiazines and phenothiazine photoproducts

Disemination

Articles

1. Udrea, A.M.; Dinache, A.; Staicu, A.; Avram, S.; "Target Prediction of 5,10,15,20-Tetrakis(4′-Sulfonatophenyl)-Porphyrin Using Molecular Docking" Pharmaceutics 14(11), 2390 (2022).

Conferences

1. AM. Udrea, A. Staicu, C.Mares, S. Avram; "Predictions of the TPPS photosensitizer pharmacodynamics as a cancer treatment using molecular docking"; ICLPR-ST 2022, 7-10, Iunie, 2022, Bucuresti, Romania

2. AM. Udrea, S. Nistorescu, ML. Pascu, MO. Romanitan, S. Avram; "In silico study of laser-irradiated PZ in interaction with the SARS-Cov-2 Mpro"; ICLPR-ST 2022, 7-10, Iunie, 2022, Bucuresti, Romania.

3. AM. Udrea, A. Staicu, S. Avram; "The interactions between photosensitizer and cancer therapeutical targets- a computational approach"; RAD 10 th Jubille, Spring Edition, 13-17, Iunie, Herceg Novi, Montenegro.

4. M. Boni, SI.Nistorescu, T.Tozar, A. Dinache, G. Stanciu, AM. Udrea, A. Simon, A.Staicu; "System for Water Treatment Based on Singlet Oxygen Micro-nanobubbles", ICLPR-ST 2022, 7-10, Iunie, 2022, Bucuresti, Romania.

5. A. Dinache, S.Nistorescu, A. Smarandache, T. Tozar, M. Boni, AM. Udrea, A. Staicu, Photophysical properties of porphyrins loaded TiO2 nanoparticles, ICLPR-ST 2022, 7-10 Iunie 2022, Bucuresti.

6. AM. Udrea, C. Mares, A. Staicu, T. Tozar, M. Pascu, S. Avram; "Fotoprodusii medicamentelor psihotrope in interactie cu transportorul de dopamina-abordare bioinformatica", Conferinta Nationala Tehnologia&IHealth in medicina secolului XXI, 6-9, Iulie, 2022, Targu Mures, Romania

7. C. Mares, AM. Udrea, S. Avram; "Bioinformatica- Tehnică de succes în proiectarea și analiza eficienței farmacologice a compușilor de sinteză și a compușilor naturali", Conferinta Nationala Tehnologia&IHealth in medicina secolului XXI, 6-9, Iulie, 2022, Targu Mures, Romania

2023

Stage 2: The phenothiazine derivative's physicochemical characterization, irradiation, and in vitro evaluation.

Objectives

Irradiation of the selected phenothiazine and determination of the temporal stability of the mixture resulting from phenothiazine after laser irradiation.

Deliverables

*Communication to a National Conference.

*Communication for an International Conference.

*An article in the yellow zone or above.

*Spectral database of the phenothiazine before and after laser irradiation.

Disemination

National Conferences

1. Ana-Maria Udrea, Angela Staicu, Speranta Avram, Madalina-Andreea Badea, Ionut-Relu Andrei, Mihail-Lucian Pascu, Patricia Preduna, Mihaela Balas. ,,Innovative Repurposing Repositioning of Chlorpromazine via Laser Irradiation: A Promising Strategy for Breast Cancer Treatment,, 1st Romanian-French Workshop on Non-Thermal Plasma PLASMA RO-FR 31 August – 1 September 2023 INFLPR, Magurele, Romania. –Prezentare Orală

International Conferences

1. Ana-Maria Udrea, Angela Staicu, Speranta Avram, Madalina-Andreea Badea, Ionut-Relu Andrei, Mihail-Lucian Pascu, Patricia Preduna, Mihaela Balas. ,,Innovative Repurposing Repositioning of Chlorpromazine via Laser Irradiation: A Promising Strategy for Breast Cancer Treatment,, 1st Romanian-French Workshop on Non-Thermal Plasma PLASMA RO-FR 31 August – 1 September 2023 INFLPR, Magurele, Romania. –Prezentare Orală

2. Angela Staicu, Mihaela Balas, Ana-Maria Udrea, Andra Dinache, Adriana Smarandache, Mihai Boni, Tatiana Tozar, Iulia Lungu, Madalina-Andreea Badea, Florian Dumitrache, Valentin Adrian Maraloiu, Petronela Prepelita. ,,Enhancing Photodynamic Therapy for Melanoma: Nanoparticle Porphyrin Complexes,, NanoInovation 2023 Conference & Exhibition, 18-22 September 2023, Rome, Italy. –Prezentare Poster.

3. Mihaela Balas, Madalina-Andreea Badea, Patricia Preduna, Angela Staicu, Ionut-Relu Andrei, Ana-Maria Udrea. ,,Laser-irradiation increases chlorpromazine antitumor activity in breast cancer cells,, Eurotox 2023, 10-13 September 2023, Ljubljana, Slovenia.- Prezentare Poster.

4. Ana-Maria Udrea, Angela Staicu, Speranta Avram, Madalina-Andreea Badea, Ionut-Relu Andrei, Mihail-Lucian Pascu, Patricia Preduna, Mihaela Balas. "Laser Irradiated Chlorpromazine-Application in Breast Cancer Treatment"; 14th EBSA congress, July 31-August 4, 2023, Stockholm, Sweden/ P495

Outreach activities

1. Ana-Maria Udrea ”Medicamente Iradiate Laser: O Nouă Abordare în Lupta Împotriva Cancerului de Sân” Prezentare Orală la Noaptea cercetătorilor 2023, Reconnect- Research for Health , 29 Septembrie 2023, Parcul Liniei, București.

Rezultatele au fost publicate în 7 articole ISI dintre care 4 în zona roșie și 3 în zona galbenă în funcţie de valoarea JIF (Journal Impact Factor), conform ediţiei JCR-2022 (iunie 2023).

Articles in red zone

1. Enache M, Andriesei BM, Oancea A, Udrea AM, Raducan A, Oancea P, Avram S. Interaction of anti-inflammatory drug nimesulide with ionic and non-ionic surfactant micelles: Insights from spectral and bioinformatics approach, Journal of Molecular Liquids; 392,1,123511, 2023. Revista Journal of Molecular Liquids se află pe poziția 4, zona Q1 JIF 2022 (JCR iunie 2023), categoria conform Web of Science Category-Index-physics, atomic, molecular & chemical–science.

2. Dumitrascu F, Caira MR, Avram S, Buiu C, Udrea AM, Vlad IM, Zarafu I, Ioniță P, Nuță DC, Popa M, Chifiriuc MC, Limban C. Repurposing anti-inflammatory drugs for fighting planktonic and biofilm growth. New carbazole derivatives based on the NSAID carprofen: synthesis, in silico and in vitro bioevaluation. Frontiers in Cellular and Infection Microbiology; 13: 1181516, 2023. Revista Frontiers in Cellular and Infection Microbiology se află pe poziția 30, zona Q1 JIF 2022 (JCR iunie 2023), categoria conform Web of Science Category-Index- microbiology–science.

3. Udrea A.M, Smarandache A, Dinache A, Mares C, Nistorescu S, Avram, S, Staicu, A. Photosensitizers-Loaded Nanocarriers for Enhancement of Photodynamic Therapy in Melanoma Treatment. Pharmaceutics; 15,2124,2023. Revista Pharmaceutics se află pe poziția 54, zona Q1 JIF 2022 (JCR iunie 2023), categoria conform Web of Science Category-Index- pharmacology & pharmacy –science.

4. Balas M, Nistorescu S, Badea MA, Dinischiotu A, Boni M, Dinache A, Smarandache A, Udrea AM, Prepelita P, Staicu A. Photodynamic Activity of TMPyP4/TiO2 Complex under Blue Light in Human Melanoma Cells: Potential for Cancer-Selective Therapy. Pharmaceutics; 15(4),1194, 2023. Revista Pharmaceutics se află pe poziția 54, zona Q1 JIF 2022 (JCR iunie 2023), categoria conform Web of Science Category-Index- pharmacology & pharmacy –science.

Articles in yelow zone

1. Bădiceanu CD, Mares C, Nuță DC, Avram S, Drăghici C, Udrea AM, Zarafu I, Chiriță C, Hovaneț MV, Limban C. N-Substituted (Hexahydro)-1H-isoindole-1,3(2H)-dione Derivatives: New Insights into Synthesis and Characterization. Processes; 11(6):1616. 2023. Revista Processes se află pe poziția 30, zona Q2 JIF 2022 (JCR iunie 2023), categoria conform Web of Science Category-Index- chemistry, medicinal–science.

2. Mareş C, Udrea AM, Şuţan NA, Avram S. Bioinformatics Tools for the Analysis of Active Compounds Identified in Ranunculaceae Species. Pharmaceuticals. 16(6):842 2023. Revista Pharmaceuticsals se află pe poziția 5, zona Q2 JIF 2022 (JCR iunie 2023), categoria conform Web of Science Category-Index- chemistry, medicinal–science.

3. Negrea E, Oancea P, Leonties A, Udrea AM, Avram S, Raducan A. Spectroscopic studies on binding of ibuprofen and drotaverine with bovine serum albumin. Journal of Photochemistry and Photobiology A: Chemistry. 438, 114512 2023. Revista Journal of Photochemistry and Photobiology A: Chemistry se află pe poziția 28, zona Q2 JIF 2022 (JCR iunie 2023), categoria conform Web of Science Category-Index- chemistry, physical –science.

2024

Stage 3: In vitro evaluation of the efficacy of the phenothiazine derivative.

Objectives

Establishing the best treatment for the MCF7 cell line

Deliverables

Articles in red or yelow zone

1. Mares C, Udrea AM, Buiu C, Staicu A, Avram S. Therapeutic Potentials of Aconite-like Alkaloids: Bioinformatics and Experimental Approaches. Mini Reviews in Medicinal Chemistry. Volume 24, Number 2, 2024, pp. 159-175(17). Reista Mini Reviews in Medicinal Chemistry se află pe poziția 14, zona Q2 JIF 2022 (JCR iunie 2023), categoria conform Web of Science Category-Index- chemistry, medicinal – science.