Comparative evaluation of methodologies for studying the in vitro cytotoxicity of theranostic nanosystems in a 3D breast cancer culture model

• Grant number: 23/13424-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2024
• End date: January 31, 2025
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Luciana Biagini Lopes
• Grantee: Giovanna Barros de Melo
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 18/13877-1 - Nanocarriers for localized treatment and chemoprevention of breast tumors, AP.JP2

Abstract

Cancer is the term used to describe a heterogeneous group of diseases, characterised by the proliferation of cells that can invade tissues and organs. Within this group is breast cancer, the cancer that most affects women worldwide. Despite that, the conventional methods of diagnosis and treatment available today are scarce and still very limited in combating the disease, which results in late diagnosis of tumours and intervention with undesirable side effects. In this scenario, theranostic nanomedicine is considered promising for tumour diagnosis and treatment, since it can creat a multifunctional nanosystem. In our group, a new hybrid nanosystem consisting of ethosomes containing co-encapsulated inorganic nanoparticles and the drug methotrexate has been developed for intraductal local application in the treatment and diagnosis of breast cancer. 3D cell models have shown an enhanced mimic of the tumour environment. However, it can bring new challenges to cytotoxicity evaluation of these novel nanosystems due to diffusion barriers, which are brought up with this model and are not seen in monolayer culture, and due to interference caused by materials used in the formulation composition. The aim of this project is to evaluate, in a comparative manner, methodologies to assess nanosystem cytotoxicity in spheroids of breast tumour cells and establish relationships between alterations in viability and penetration kinetics provided by the nanosystem. Our research aims to understand the influence of the nanosystem and its concentration on the cell viability of spheroids and to contribute to the development of theranostics and localised treatments for breast cancer.