Analysis of pyroptosis and necroptosis induced by 5-ALA-mediated photodynamic and sonodynamic therapies in oral squamous cell carcinoma: an in vitro study

• Grant number: 25/09848-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2025
• End date: August 31, 2026
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Luciana Corrêa
• Grantee: Laura Barduchi de Andrade
• Host Institution: Faculdade de Odontologia (FO). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Oral squamous cell carcinoma (OSCC) is the most common malignant neoplasm of the oral cavity, characterized by a high invasive potential and frequent recurrences, making its treatment a clinical challenge. Photodynamic therapy (PDT) has emerged as a promising alternative to conventional treatment; however, the underlying mechanisms of regulated cell death induction, particularly pyroptosis and necroptosis, are not yet fully understood. Additionally, sonodynamic therapy (SDT) has shown promising efficacy in preclinical studies for the treatment of various malignant neoplasms, and its combination with PDT, known as sono-photodynamic therapy (SPDT), may enhance this efficacy. This study aims to investigate, in vitro, the activation of pyroptosis and necroptosis in OSCC cells treated with 5-aminolevulinic acid-mediated PDT. The analysis will be conducted through the evaluation of morphological and ultrastructural aspects, quantification of lactate dehydrogenase release, and immunofluorescence detection of gasdermin D and MLKL. By doing so, this study seeks to elucidate the mechanisms of regulated cell death induced by PDT in OSCC, contributing to the development of more effective therapeutic approaches. (AU)