Synthesis and characterization of water-soluble NaGdF4:Yb/Tm@NaGdF4:Tb@YF4 nanocrystals functionalized with cetuximab for application in photodynamic therapy

• Grant number: 25/02962-1
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: July 01, 2025
• End date: February 28, 2029
• Field of knowledge: Physical Sciences and Mathematics - Physics - Condensed Matter Physics
• Principal Investigator: Leandro José Raniero
• Grantee: Vitor Luca Moura Marmo
• Host Institution: Instituto de Pesquisa e Desenvolvimento (IP&D). Universidade do Vale do Paraíba (UNIVAP). São José dos Campos , SP, Brazil

Abstract

The project proposes the synthesis of multilayer nanocrystals with the NaGdF¿:Yb/Tm@NaGdF4:Tb@NaYF4 structure for application in photodynamic therapy (PDT). These nanocrystals act as upconversion nanostructures (UCNPs), converting near-infrared (NIR) energy into emission in the UV-visible spectrum, enabling the conversion of molecular oxygen to singlet oxygen (1O2). In addition, they will be functionalized with cetuximab (CX) IgG monoclonal antibodies to increase specificity to tumor cells with overexpression of the epidermal growth factor receptor (EGFR). The synthesis will be performed using the thermal decomposition methodology, which provides better results in converting near-infrared radiation into radiation in the UV-visible spectral range. Structural, colloidal and optical characterization studies will be carried out. Although these nanocrystals are insoluble in aqueous media, the reaction is intended to be performed with the Lemieux-von Rudloff reagent, which will replace oleic acid with azelaic acid, making it water-soluble. In this way, covalent binding to antibodies via carbodiimide reaction will be feasible later, due to the carboxylic groups at their ends. Cytotoxicity studies will be conducted using MDA-MB-468 triple-negative breast cancer tumor lines. Thus, the nanocrystals are expected to present high colloidal stability and optimized energy efficiency, allowing their activation in deeper regions compared to PDT with conventional photosensitizers. The combination of PDT with functionalized nanocrystals should have greater therapeutic efficacy and reduced adverse effects, expanding the possibilities of nanomedicine in the field of oncology.