Antibody nanoprobes for Cancer treatment by photodynamic therapy

• Grant number: 22/07411-5
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2023
• End date: November 30, 2025
• Field of knowledge: Health Sciences - Collective Health - Public Health
• Principal Investigator: Leandro José Raniero
• Grantee: Leandro José Raniero
• Host Institution: Instituto de Pesquisa e Desenvolvimento (IP&D). Universidade do Vale do Paraíba (UNIVAP). São José dos Campos , SP, Brazil
• Associated researchers: Cristina Pacheco Soares ; Juliana Ferreira Strixino

Abstract

Cancer corresponds to more than one hundred different types of malignant neoplasms, and the molecular analysis of the expression of oncoproteins is important for the patient's prognosis, as they act in the cellular signaling/regulation pathways involved in the disease evolution. Thus, the overexpression of the epithelial growth receptor (HER1) is linked to a worse prognosis, present in some of the malignant tumors such as lung, colon, prostate and breast. Among these types, the one with the highest incidence and fatality in women is breast carcinoma with 29.7% of cases estimated for the triennium 2020-2022, which has unfavorable prognosis when associated with HER1 receptor overexpression. Thus, the improvement/development of new methods to increase the efficiency of treatments is a public health issue. In this context, Photodynamic Therapy (PDT) is a therapeutic modality that presents good results in the treatment of cancer, standing out for the absence of cumulative toxicity. PDT is based on the interaction of the photosensitizer (FS) with malignant tumor cells, followed by tissue irradiation with an adequate wavelength and in the presence of molecular oxygen, giving rise to reactive species that promote cell death. Therefore, the specificity of the FS is fundamental for the success of the treatment without affecting normal tissues, increasing the efficiency of the treatment. Therefore, in this project we intend to synthesize antibody nanoprobes composed of modified HER1 antibodies loading gold nanoparticles functiolalized Chlorine e6, focusing on breast cancer treatment via PDT. Thus, an increase in PDT specificity is expected in malignant tumors that overexpress HER1, playing a dual role by blocking the epithelial growth factor protein, which binds to the HER1 receptor and increases cell proliferation. These nanoprobes will be synthesized and characterized by Spectroscopies techiniques such as Raman, FTIR and Mass . Colloidal stability will be studied by Dynamic Light Scattering as a function of the pH of the medium as wellas saline solution. In vitro assays will allow to evaluate the nanoprobes cytotoxicity. PDT will be evaluated in 2D and 3D cell culture in human breast carcinoma cell line (MDA-MB-468) that has HER1 overexpression and normal human breast (MCF 10A). Assays will be performed to determine the reactive oxygen species and the type of cell death caused in PDT associated with antibody nanoprobes. (AU)