Targeted Phototherapeutic Impact of Antibody- Functionalized Gold Nanostructures Conjugated with Methylene Violet on Skin Cancer Cells

• Grant number: 24/05366-8
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: September 01, 2024
• End date: August 31, 2025
• Field of knowledge: Engineering - Materials and Metallurgical Engineering - Nonmetallic Materials
• Principal Investigator: Pedro Henrique Benites Aoki
• Grantee: Mirella Boaro Kobal
• Supervisor: Christelle Prinz
• Host Institution: Faculdade de Ciências e Letras (FCL-ASSIS). Universidade Estadual Paulista (UNESP). Campus de Assis. Assis , SP, Brazil
• Institution abroad: Lund University, Lund, Sweden
• Associated to the scholarship: 21/14500-1 - Towards convergence of photodynamic (TFD) and photothermal (TFT) therapies on in vitro culture of melanoma-derived cells, BP.DR

Abstract

Cancer remains a predominant global health challenge, significantly impacting thousands of lives worldwide. Among various cancer types, skin cancer represents a considerable fraction of diagnoses, with melanoma carcinomas constituting 21% of these cases. Despite their relatively low incidence, melanomas are notably lethal, exhibiting a mortality-to-incidence ratio of 17.6%. Conventional cancer treatments often fall short due to adverse side effects and the emergence of drug resistance, prompting the investigation of alternative therapeutic modalities, such as light-based therapies. Photodynamic therapy (PDT) leverages light-activated photosensitizers (PS) to produce reactive oxygen species (ROS), selectively targeting and eradicating tumor cells. In contrast, photothermal therapy (PTT) operates independently of oxygen levels, rendering it effective against hypoxic tumors by converting light into heat upon activation, subsequently elevating local temperatures to eliminate cancerous tissue. Innovatively, photothermal agents like gold-shell isolated nanoparticles (AuSHINs) can be combined with PS molecules to create synergistic nanostructures that amplify therapeutic outcomes, inflicting more extensive damage on malignant tissues. This study proposes the development of such synergistic nanostructures by conjugating AuSHINs with the PS methylene violet 3RAX (VM), yielding AuSHINs@VM@. To enhance specificity towards melanoma cells, these nanostructures will be further functionalized with CD146 antibodies (AuSHINs@VM@Ab), specified to tumor cells, include melanoma. The research aims to evaluate the combined effects of PDT and PTT, along with the targeted action of AuSHINs@VM@Ab on melanoma skin cancer cells (A375 cell line). The efficacy of these nanostructures will be assessed through flow cytometry and confocal fluorescence microscopy to A375 cells after incubation with AuSHINs@VM@Ab, providing insights into their potential as a targeted, dual-modality treatment for melanoma.