Development of Hydrogel-based Phototheranostic Systems with Targeted Action on Breast Cancer

Project code:
PN-IV-P2-2.1-TE-2023-1059
Contract number:
5TE/2025
Founded by:
MEC, ANC, UEFISCDI
Program:
Research projects to stimulate young independent teams
Contractor:
National Institute for Laser, Plasma and Radiation Physics
Project Leader:
Tatiana Tozar
Start date:
08.01.2025
End Date:
31.12.2026
Summary

Breast cancer is a significant health issue with high incidence worldwide. Current treatment approaches face challenges such as therapy resistance, invasiveness of biopsy, non-specific toxicity of chemotherapy, and damage to healthy tissues by radiation therapy. To overcome these challenges, the proposed project aims to develop hydrogel-based phototheranostic systems for targeted breast cancer treatment. This interdisciplinary approach combines photodynamic therapy with hydrogel drug delivery systems to provide real-time diagnosis and concurrent treatment. the photosensitizer used is Motexafin lutetium (MLu) due to its fluorescence emission and singlet oxygen generation capabilities. Motexafin lutetium can be activated by 732 nm light, enabling deeper tissue penetration.

The project involves two stages: development and evaluation of phototheranostic systems, and characterization and in vitro evaluation of hydrogel systems. Activities include designing irradiation systems, characterizing motexafin lutetium and hydrogels, optimizing parameters, and evaluating therapeutic efficacy. The proposed systems aim to enhance selectivity, and controlled drug delivery while minimizing systemic toxicity. By addressing the limitations of current approaches, this project offers originality, innovation, and potential advancements in breast cancer treatment.

Cognitive and Socio-Economic Impact

The project has generated both significant cognitive and socio-economic impact by advancing fundamental knowledge and enabling future applications in photodynamic therapy and smart biomaterials. Scientifically, it has clarified the photophysical behavior of motexafin lutetium (MLu), demonstrating a high singlet oxygen quantum yield and positioning MLu as a highly efficient photosensitizer for breast cancer phototherapy, while also establishing experimental methodologies and custom optical setups for real-time monitoring of singlet oxygen and laser-induced hydrogel photopolymerization. At the same time, the project has provided an integrated framework linking irradiation parameters, hydrogel network structure, residual photoinitiator content, and MLu release kinetics, thus defining optimal processing windows for several MLu-loaded hydrogel formulations. Socio-economically, these results open a path toward minimally invasive, localized treatments with reduced side effects and potential cost savings for cancer care, and offer transferable know-how for other biomedical and industrial applications involving photocrosslinked hydrogels. The creation of dedicated experimental infrastructure, the training of young researchers, participation in international conferences, preparation of a scientific manuscript, and drafting of a patent application further strengthen the institution’s research capacity and its potential for innovation and technology transfer.

Expected results

The project's scientific results are focused on the development and characterization of hydrogel-based phototheranostic systems using MLu as a photosensitizer in view of targeted therapeutic action against breast cancer. The expected result indicators include:

• Characterization of MLu exposed to laser radiation, including fluorescence and singlet oxygen measurements.

• Formation of hydrogels using poly(vinyl alcohol), poly(ethylene glycol), and their combinations, through photo-polymerization.

• Evaluation of the physical and chemical properties of the hydrogels using spectroscopic techniques, microscopy, and contact angle measurements.

• Characterization of MLu hydrogel systems, including monitoring of fluorescence and singlet oxygen generation.

• Release studies of MLu from the hydrogels and evaluation of therapeutic efficacy using in vitro assays.

Obtained results

Project Team
Project Leader:
Tatiana Tozar, Project Leader
Team member:
Angela Staicu, Researcher
Team member:
Ionut Relu Andrei, Postdoctoral Researcher
Team member:
Smarandache Adriana, Postdoctoral Researcher
Team member:
Andra Dinache, Postdoctoral Researcher
Team member:
Mihai Boni, Postdoctoral Researcher
Team member:
Vacant position, PhD student member
Team member:
Vacant position, Researcher

Stage Reports

January 2025 - December 2025

Stage 1: Development and evaluation of phototheranostic systems. (January 2025 - December 2025)

Scientific Report TE1059 Stage 1

Objectives:

- Development and implementation of irradiation systems.

- Evaluation of motexafin lutetium.

- Formation of the hydrogel systems

- Analysis and optimization

Deliverables:

1. Design of the irradiation system for motexafin lutetium irradiation; 2. Design of the irradiation system construction for hydrogel fabrication; 3. Fluorescence data on motexafin lutetium exposed to laser radiation. 4. Singlet oxygen data on motexafin lutetium exposed to laser radiation; 5. Hydrogel-based phototheranostic systems; 6. Web page; 7. Two scientific communications – international/national conference; 8. One article in preparation; 9. Stage report.

Dissemination:

Conferences

1. T. Tozar, M. Boni, S. Nistorescu, A. Staicu “Laser-induced photo-crosslinking of hydrogel for controlled release”, E-MRS Spring Meeting 2025, Strasbourg, France 26-30 May 2025 (poster presentation)

2. T. Tozar, M. Boni, A. Staicu, A. Dinache, “Development and characterization of motexafin lutetium-loaded hydrogels for NIR-activated photodynamic therapy in breast cancer”, SHIFT 2025, San Cristóbal de La Laguna, Spain, 13-17 October 2025 (oral presentation)

Articles

1. Article in preparation

Patents

1. Romanian patent application in preparation

January 2026 - December 2026

Stage 2: In-depth characterization and in vitro evaluation of phototheranostic hydrogel systems. (January 2026 - December 2026)

Objectives:

- Characterization of phototheranostic hydrogel systems

- In vitro therapeutic evaluation on breast cancer cells

- Analysis and optimization

Deliverables:

1. design of irradiation system for monitoring fluorescence and singlet oxygen generation; 2. release studies of motexafin lutetium from the hydrogels; 3. phototheranostic hydrogel systems; 4. development of the irradiation and fluorescence monitoring system for in vitro evaluation; 5. in vitro evaluation of therapeutic efficacy of the phototheranostic hydrogel systems; 6. two scientific communications – international/national conference; 7. two article in peer-reviewed journals ranked Q1; 8. final report; 9. project web page - update