Development of thermoresponsive hydrogels loaded with Chlorin e6 for potential application in Photodynamic Therapy for melanoma

• Grant number: 25/03000-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2025
• End date: August 31, 2026
• Field of knowledge: Engineering - Biomedical Engineering - Bioengineering
• Principal Investigator: Fernando Lucas Primo
• Grantee: Isabelle Freitas de Paiva
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Contemporary science has revolutionized the understanding and treatment of diseases, particularly skin cancer, such as melanoma, which is highly aggressive and prone to metastasis. One promising approach for treatment is Photodynamic Therapy (PDT), which involves the use of photosensitizers (PS) and light emission at a specific wavelength to generate reactive oxygen species (ROS), inducing apoptosis in tumor cells. Chlorin e6, a second-generation PS approved by the FDA for the treatment of certain types of cancer, has shown efficacy in tumor control. However, its low solubility in aqueous media limits its application due to reduced interaction in biological environments. To overcome this limitation, the present project proposes the use of thermoreversible hydrogel systems based on nanoemulsions to solubilize and deliver Chlorin e6. A low-energy-input methodology will be employed for the synthesis of the nanoemulsions, and system stability will be evaluated based on the behavior of the nanoemulsions in relation to different surfactants. The physicochemical properties of the hydrogel will be analyzed using Dynamic Light Scattering (DLS), Cryo-Scanning or Transmission Electron Microscopy (Cryo-STEM), and rheological analysis with an oscillatory rheometer. The biological activity will be tested on human malignant melanoma cell lines (A-375 or SK-Mel) cultured in monolayer. The safety and efficacy of the thermoreversible hydrogel system will be assessed through cellular uptake and cytotoxicity assays, as well as cell viability after treatment using Photodynamic Therapy (PDT). The aim of this project is to develop and characterize an advanced thermoreversible hydrogel system based on Chlorin e6 nanoemulsions, focusing on improving the effectiveness of Photodynamic Therapy as an adjuvant treatment for skin cancer.