Development of microfluidic devices (tumor-on-a-chip) for evaluation of nanostructured systems associated with photodynamic therapy of 3D tumor models of gliomas

• Grant number: 24/18204-6
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2025
• End date: September 30, 2028
• Field of knowledge: Engineering - Biomedical Engineering - Bioengineering
• Principal Investigator: Fernando Lucas Primo
• Grantee: Fernando Lucas Primo
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated researchers: Liam Grover ; Sonia Maria Oliani

Abstract

Gliomas are rare brain tumors that originate from malignant alterations of glial cells. They are aggressive cancers with high mortality, high recurrence rates and short patient survival time, estimated at 15 months. Surgical treatment is the gold standard, with maximum tumor resection, in addition to radiotherapy and chemotherapy, which are commonly used, either alone or in combination with tumor resection. However, these treatments are often unable to provide a cure, either because the resection surgery is unable to remove all of the tumor content due to the extent of the lesion, or because of the presence of glioma stem cells that contribute to disease recurrence. In addition, the blood-brain barrier poses an additional challenge in treatment, as it hinders the access of several chemotherapy drugs, administered orally or parenterally, reducing the effectiveness of drug treatments. In this context, photodynamic therapy is presented as a minimally invasive alternative therapy that complements traditional treatments already used for brain cancer, since it is possible to administer the photosensitizer followed by the application of light locally, directly on the lesion during tumor resection surgery using microcannulas and/or fiber optic bundles. For this, it is necessary to use photosensitizing substances that often have low solubility or low stability in aqueous systems, which becomes a limiting factor for their use. Therefore, the development of nanoemulsified systems is an excellent strategy to overcome the limitation of stability and solubility in an aqueous environment. In addition, it can promote better physical-chemical stability and consequently greater photodynamic potential. When it comes to the development of cancer therapies, the use of animals has been the model for biomedical research. However, due to bioethical issues regarding animal welfare and evidence of low predictability in comparing data obtained in animals with effects on humans, it was realized that there was a need to develop alternative in vitro methods capable of mimicking the human organism, in addition to being in line with the Russell-Burch Principles, also known as the 3 R's Principle, which consists of "reduction, replacement and refinement" in the use of animals. In this context, microfluidics has been gaining prominence, since it has shown itself to be potentially viable for biomedical applications, especially in studies replacing the use of animals. Therefore, the objective of this project is to develop microfluidic devices (tumor-on-a-chip) of 3D tumor models of gliomas and non-tumor cells to evaluate the safety and efficacy of photosensitizing actives incorporated into nanoemulsified systems, obtained by a low-energy input method, without the use of heating and organic solvents, associated with photodynamic therapy, as an alternative study platform to the use of animals to evaluate the safety and efficacy of new complementary therapies for the treatment of brain tumors. (AU)