Understanding the Role of the Biomolecular Corona in the Biological Effect of Gold Nanoparticles

• Grant number: 25/03023-9
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: August 31, 2025
• End date: August 30, 2026
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Marcelo Bispo de Jesus
• Grantee: Luana Pereira Cardoso
• Supervisor: Aled Clayton
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: Cardiff University, Wales
• Associated to the scholarship: 22/09892-0 - Investigations of the therapeutic and cytotoxic effects of metallic nanoparticles under the influence of biomolecular coronas, BP.DR

Abstract

Breast cancer is the second leading cause of cancer-related deaths globally, and despite existing treatments, there remains a need to deepen understanding and refine therapeutic strategies. One promising approach is photothermal therapy (PTT), a minimally invasive treatment where photothermal agents, like gold nanoparticles, convert light into heat, raising the temperature of target tissues and inducing cell death. However, when administered intravenously, these nanoparticles interact with blood macromolecules, forming a biomolecular corona that changes their biological identity. Corona formation depends on the nanoparticles' properties and the serum composition, which is influenced by the patient's pathological condition. Thus, it is crucial to understand how cancer patient serum affects the biological response of nanoparticles, including photothermal therapy. Our project, designed for an exchange program, proposes an innovative approach to explore the relationship between patient profiles and nanoparticle toxicity. We will utilize serum from breast cancer patients at various stages, as well as tumor cells, adjacent non-tumor cells, and blood-derived macrophages. First, we will incubate nanoparticles with patient serum to induce corona formation. Next, we will apply nanoparticles with and without the corona to primary cells, followed by near-infrared laser treatment. Cytotoxicity and nanoparticle internalization will be assessed, and endocytic pathways will be investigated through selective inhibition of internalization mechanisms and exosomes secretion. Additionally, proteins in the nanoparticle corona will be identified via liquid chromatography-mass spectrometry (LC-MS/MS). This study aims to clarify how serum influences nanoparticle cytotoxicity, recognizing that tumors significantly alter serum composition and, consequently, corona formation. Through this targeted approach, we aim to gain deep insights into the role of the biomolecular corona in the effectiveness of photothermal therapy.