Functionalized gold nanostars for specific photothermal therapy of colorectal cancer: studies in membrane models and cell cultures

Abstract

Colorectal cancer currently ranks third in incidence and is the second leading cause of death worldwide. Traditional treatment modalities, such as chemotherapy and radiotherapy, generate severe side effects, highlighting the need for new therapeutic approaches. In this context, photothermal therapy (PTT) has stood out for its effectiveness in reducing the viability of tumor cells. However, this approach also affects non-tumor cells, underscoring the need for new strategies that offer a more specific and selective treatment. In this doctoral project, gold nanostars coated with silica (AuSHINST) and functionalized with antibodies (AuSHINST_Ab) will be synthesized, aiming at the specific PTT of cells derived from colorectal carcinoma (Caco-2 and HT-29). Bioinspired cellular membrane systems will be constructed using Langmuir and Langmuir-Schaefer (LS) films to unravel the interaction mechanisms and photothermal effects responsible for cellular toxicity. The films will be fabricated from cell lipid extracts and characterized by surface pressure vs. area measurements (À-A isotherms) and Fourier-transform infrared spectroscopy (FTIR). Furthermore, we will evaluate the photothermal efficiency and specificity of the nanostructures in in vitro cultures of Caco-2 and HT-29, comparing them with non-tumor cells. Flow cytometry and confocal microscopy will be the main techniques used to characterize the in vitro systems. We will also investigate the effects of nanostructure photoactivation in 3D cell cultures, increasing the complexity of the systems studied and more closely approximating in vivo conditions. By the end of the project, we aim to gain knowledge not only about the photothermal efficiency and specificity of AuSHINST_Ab in colorectal cancer but also to uncover the cell death pathways activated by PTT and understand the underlying mechanisms of the photochemical reactions triggered. This doctoral project is linked to the Thematic Project No. 2018/22214-6.