Gold Nano-Bio-Interaction to Modulate Mechanobiological Responses for Cancer Therapy Applications Ahmad Sohrabi Kashani, Kevin Larocque, Alisa Piekny, and Muthukumaran Packirisamy* Cite This: ACS Appl. Bio Mater. 2022, 5, 3741-3752 Read Online ACCESS Metrics & More Article Recommendations * sı Supporting Information ABSTRACT: In the present study, we investigate the mechano- biological responses of human lung cancer that may occur through their interactions with two diferent types of gold nanoparticles: nanostars and nanospheres. Hyperspectral images of nanoparticle- treated cells revealed diferent spatial distributions of nanoparticles in cells depending on their morphology, with nanospheres being more uniformly distributed in cells than nanostars. Gold nano- spheres were also found to be more efective in mechanobiological modulations. They signifcantly suppressed the migratory ability of cells under diferent incubation times while lowering the bulk stifness and adhesion of cells. This in vitro study suggests the potential applications of gold nanoparticles to manage cell migration. Nano-bio-interactions appeared to impact the cytoske- letal organization of cells and consequently alter the mechanical properties of cells, which could infuence the cellular functions of cells. According to the results and migratory index model, it is thought that nanoparticle-treated cells experience mechanical changes in their body, which largely reduces their migratory potentials. These fndings provide a better understanding of nano-bio-interaction in terms of cell mechanics and highlight the importance of mechanobiological responses in designing gold nanoparticles for cancer therapy. KEYWORDS: Nano-bio-interaction, Migratory index, Cell mechanics, Gold nanomedicines, Atomic force microscopy 1. INTRODUCTION Gold nanoparticles have attractive physiochemical properties, and several studies have been conducted to investigate their interactions with a variety of cancer cell lines to develop their implications for diagnosis, treatment, and prevention. 1−3 In those nano-bio-interaction (NBI) studies, the focus has mostly been on cellular uptake and cytotoxicity of nanoparticles (NPs) and their intracellular fate. However, the mechanobio- logical changes that might occur during NBI have received less attention. During metastasis, which is the primary cause of cancer-related mortality, the mechanobiological properties 4 of cells, such as stifness and adhesion, are signifcantly changed, enabling them to facilitate their motility and invasiveness. 5−9 These changes in the mechanobiological properties of cancer cells stem from alterations in their cytoskeletal organization. Changes in the mechanobiological properties of cells during cancer progression infuence their interpretation of forces from the surrounding environment, which may allow them to migrate more efectively. 10−13 In recent years, a few studies revealed the potential use of NPs to infuence the mechanobiology of cancer cells, particularly cell stifness and cell migration. They hypothesized that by suppressing cancer cell migration, NPs could be used to block metastasis. 6,14−16 After cellular uptake, NPs could escape from lysosomal and endosomal compartments where they have opportunities to interact with the cytoskeleton. 17 One hypothesis is that they disturb cytoskeletal organization or interfere with force generation and afect cell migration. 18,19 Furong et al. 20 showed morphological changes in human fbroblast cells after interaction with single-walled carbon nanotubes. They observed that these nanomaterials directly interact with actin networks after entering cells. Diferent parameters such as size, morphology, surface chemistry, NPs concentration, incubation time, and cell type can infuence how NPs interact with cytoskeletal structures. 21 For example, Yang and co-workers 18 showed that the migration of prostate carcinoma cells is reduced in the presence of gold NPs, while the migration of human dermal fbroblasts (HDF) is dependent on surface charges and shape of gold NPs. Mironava et al. 22 showed that cellular uptake of gold NPs could disrupt the flamentous structures of HDF cells Received: March 14, 2022 Accepted: June 30, 2022 Published: July 15, 2022 Article www.acsabm.org © 2022 American Chemical Society 3741 https://doi.org/10.1021/acsabm.2c00230 ACS Appl. Bio Mater. 2022, 5, 3741−3752 Downloaded via MCGILL UNIV on October 4, 2022 at 04:01:09 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.