Enhancing Phototoxicity in Human Colorectal Tumor Cells Through Nanoarchitectonics for Synergistic Photothermal and Photodynamic Therapies

Author(s)

de Almeida Jr, Alexandre Mendes ; Ferreira, Andree Satoshi ; Camacho, Sabrina Aleessio ; Moreira, Lucas Gontijo ; de Toledo, Karina Alves ; Oliveira, Osvaldo N. ; Aoki, Pedro Henrique Benites

• Document type: Journal article
• Source: ACS APPLIED MATERIALS & INTERFACES; v. 16, n. 18, p. 10-pg., 2024-04-23.

Abstract

Phototherapies are promising for noninvasive treatment of aggressive tumors, especially when combining heat induction and oxidative processes. Herein, we show enhanced phototoxicity of gold shell-isolated nanorods conjugated with toluidine blue-O (AuSHINRs@TBO) against human colorectal tumor cells (Caco-2) with synergic effects of photothermal (PTT) and photodynamic therapies (PDT). Mitochondrial metabolic activity tests (MTT) performed on Caco-2 cell cultures indicated a photothermal effect from AuSHINRs owing to enhanced light absorption from the localized surface plasmon resonance (LSPR). The phototoxicity against Caco-2 cells was further increased with AuSHINRs@TBO where oxidative processes, such as hydroperoxidation, were also present, leading to a cell viability reduction from 85.5 to 39.0%. The molecular-level mechanisms responsible for these effects were investigated on bioinspired tumor membranes using Langmuir monolayers of Caco-2 lipid extract. Polarization-modulation infrared reflection-absorption spectroscopy (PM-IRRAS) revealed that the AuSHINRs@TBO incorporation is due to attractive electrostatic interactions with negatively charged groups of the Caco-2 lipid extract, resulting in the expansion of surface pressure isotherms. Upon irradiation, Caco-2 lipid extract monolayers containing AuSHINRs@TBO (1:1 v/v) exhibited ca. 1.0% increase in surface area. This is attributed to the generation of reactive oxygen species (ROS) and their interaction with Caco-2 lipid extract monolayers, leading to hydroperoxide formation. The oxidative effects are facilitated by AuSHINRs@TBO penetration into the polar groups of the extract, allowing oxidative reactions with carbon chain unsaturations. These mechanisms are consistent with findings from confocal fluorescence microscopy, where the Caco-2 plasma membrane was the primary site of the cell death induction process. (AU)

• FAPESP's process: 18/14692-5 - Photothermal therapy mediated by gold nanoparticles: from model systems of biomembranes toward in vitro culture of tumor cells
• Grantee: Sabrina Aléssio Camacho
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 20/15854-9 - Modulating photochemical reactions in Escherichia coli lipid monolayers with the binding mechanisms of eosin decyl ester and toluidine blue-O photosensitizers
• Grantee: Lucas Gontijo Moreira
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 14/11408-3 - Multi-User Equipment approved in grant 2013/14262-7: confocal microscope
• Grantee: Osvaldo Novais de Oliveira Junior
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 22/02189-2 - Plasmonic nanostructures for synergistic photodynamic (PDT) and photothermal (PTT) therapy of cancer cells
• Grantee: Pedro Henrique Benites Aoki
• Support Opportunities: Research Grants - Initial Project
• FAPESP's process: 18/22214-6 - Towards a convergence of technologies: from sensing and biosensing to information visualization and machine learning for data analysis in clinical diagnosis
• Grantee: Osvaldo Novais de Oliveira Junior
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 21/14500-1 - Towards convergence of photodynamic (TFD) and photothermal (TFT) therapies on in vitro culture of melanoma-derived cells
• Grantee: Mirella Boaro Kobal
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 23/01999-3 - Photoinduced modifications triggered by rose bengal in bioinspired and in vitro systems
• Grantee: André Satoshi Ferreira
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree