Quantification of cellular associated graphene and induced surface receptor responses

Nima, Zeid A.; Vang, Kieng B.; Nedosekin, Dmitry A.; Kannarpady, Ganesh K.; Saini, Viney; Bourdo, Shawn E.; Majeed, Waqar; Watanabe, Fumiya; Darrigues, Emilie; Alghazali, Karrer M.; Alawajji, Raad A.; Petibone, Dayton M.; Ali, Syed F.; Biriş, Alexandru R.; Casciano, Daniel A.; Ghosh, Anindya; Salamo, Gregory J.; Zharov, Vladimir P.; Biris, Alexandru S.

doi:10.1039/c8nr06847j

Cited by 10 publications

(15 citation statements)

References 46 publications

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“…46 These vibrational modes observed in FTIR, coupled with results from Raman and XPS confirm that the synthesized form of graphene nanoparticles are indeed LOG as described previously. 24,38,47…”

Section: Pristine Graphene Was Functionalized To Produce Log Nanopartmentioning

confidence: 99%

<p>Functionalized Graphene Nanoparticles Induce Human Mesenchymal Stem Cells to Express Distinct Extracellular Matrix Proteins Mediating Osteogenesis</p>

Newby¹,

Masi²,

Griffin³

et al. 2020

IJN

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Purpose: The extracellular matrix (ECM) labyrinthine network secreted by mesenchymal stem cells (MSCs) provides a microenvironment that enhances cell adherence, proliferation, viability, and differentiation. The potential of graphene-based nanomaterials to mimic a tissue-specific ECM has been recognized in designing bone tissue engineering scaffolds. In this study, we investigated the expression of specific ECM proteins when human fat-derived adult MSCs adhered and underwent osteogenic differentiation in the presence of functionalized graphene nanoparticles. Methods: Graphene nanoparticles with 6-10% oxygen content were prepared and characterized by XPS, FTIR, AFM and Raman spectroscopy. Calcein-am and crystal violet staining were performed to evaluate viability and proliferation of human fat-derived MSCs on graphene nanoparticles. Alizarin red staining and quantitation were used to determine the effect of graphene nanoparticles on osteogenic differentiation. Finally, immunofluorescence assays were used to investigate the expression of ECM proteins during cell adhesion and osteogenic differentiation. Results: Our data show that in the presence of graphene, MSCs express specific integrin heterodimers and exhibit a distinct pattern of the corresponding bone-specific ECM proteins, primarily fibronectin, collagen I and vitronectin. Furthermore, MSCs undergo osteogenic differentiation spontaneously without any chemical induction, suggesting that the physicochemical properties of graphene nanoparticles might trigger the expression of bone-specific ECM. Conclusion: Understanding the cell-graphene interactions resulting in an osteogenic niche for MSCs will significantly improve the application of graphene nanoparticles in bone repair and regeneration.

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Section: Pristine Graphene Was Functionalized To Produce Log Nanopartmentioning

confidence: 99%

<p>Functionalized Graphene Nanoparticles Induce Human Mesenchymal Stem Cells to Express Distinct Extracellular Matrix Proteins Mediating Osteogenesis</p>

Newby¹,

Masi²,

Griffin³

et al. 2020

IJN

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“…We checked for inflammatory cytokines and activation markers, as graphene thin films were found to affect cell surface receptors in JAWSII mouse bone marrow dendritic cells. [ 19 ] Stress response pathways, such as autophagy, were also investigated, as the latter represents an important protective mechanism that is triggered under conditions of intracellular stress, occurring during the encounters with nanomaterials. [ 20 ]…”

Section: Introductionmentioning

confidence: 99%

Comparative Effects of Graphene and Molybdenum Disulfide on Human Macrophage Toxicity

Lin

Lucherelli

et al. 2020

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Graphene and other 2D materials, such as molybdenum disulfide, have been increasingly used in electronics, composites, and biomedicine. In particular, MoS2 and graphene hybrids have attracted a great interest for applications in the biomedical research, therefore stimulating a pertinent investigation on their safety in immune cells like macrophages, which commonly engulf these materials. In this study, M1 and M2 macrophage viability and activation are mainly found to be unaffected by few‐layer graphene (FLG) and MoS2 at doses up to 50 µg mL−1. The uptake of both materials is confirmed by transmission electron microscopy, inductively coupled plasma mass spectrometry, and inductively coupled plasma atomic emission spectroscopy. Notably, both 2D materials increase the secretion of inflammatory cytokines in M1 macrophages. At the highest dose, FLG decreases CD206 expression while MoS2 decreases CD80 expression. CathB and CathL gene expressions are dose‐dependently increased by both materials. Despite a minimal impact on the autophagic pathway, FLG is found to increase the expression of Atg5 and autophagic flux, as observed by Western blotting of LC3‐II, in M1 macrophages. Overall, FLG and MoS2 are of little toxicity in human macrophages even though they are found to trigger cell stress and inflammatory responses.

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“…Nanoparticles can have specific light interaction characteristics, making them suitable for multimodal detection, such as Raman spectroscopy [27][28][29] , photoacoustic analysis 30 , magnetic resonance imaging 31 , two-photon microscopy 32 , or even a combination of these methods 33 , in 2D, 3D and in-vivo models 34 . However, few of these techniques have been applied in 3D cancer models (spheroids or phantoms) 35 .…”

mentioning

confidence: 99%

Tracking Gold Nanorods’ Interaction with Large 3D Pancreatic-Stromal Tumor Spheroids by Multimodal Imaging: Fluorescence, Photoacoustic, and Photothermal Microscopies

Darrigues

Nima

Nedosekin

et al. 2020

Sci Rep

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pancreatic cancer is one of the most complex types of cancers to detect, diagnose, and treat. However, the field of nanomedicine has strong potential to address such challenges. When evaluating the diffusion and penetration of theranostic nanoparticles, the extracellular matrix (ECM) is of crucial importance because it acts as a barrier to the tumor microenvironment. in the present study, the penetration of functionalized, fluorescent gold nanorods into large (>500 μm) multicellular 3D tissue spheroids was studied using a multimodal imaging approach. the spheroids were generated by coculturing pancreatic cancer cells and pancreatic stellate cells in multiple ratios to mimic variable tumor-stromal compositions and to investigate nanoparticle penetration. fluorescence live imaging, photothermal, and photoacoustic analysis were utilized to examine nanoparticle behavior in the spheroids. Uniquely, the nanorods are intrinsically photoacoustic and photothermal, enabling multiimaging detection even when fluorescence tracking is not possible or ideal. Nanomedicine for cancer treatments-the use of nanosized structures in cancer therapeutics and/or imaginghas been heavily investigated over the last two decades 1. Nano-sized delivery systems are useful theragnostic agents for enhanced tumor penetration, accumulation, and targeting potency. Studies of nanoparticle (NP)-based therapies have mainly focused on targeted cancer cell treatment but also include cancer stem cells 2 , stromal cancer microenvironment 3-5 , and/or cellular immune system 6,7. As a physical barrier that limits NP penetration and distribution, the extracellular matrix (ECM) is a crucial concern when evaluating the effects of nanoscale cancer therapies. Recent work showed that the ECM can be regulated by using gold NPs to interrupt the crosstalk between cancer cells and stellate cells, which reeducates the stellate cells 8,9. However, the development of nanosystems for cancer treatment has been hampered by the limitations of current in vitro models, which are generally based on two-dimensional (2D) cell cultures. These 2D models struggle to provide an accurate representation of the in vivo environment and its components, which include the dynamic tumor microenvironment (TME), cell heterogeneity, and nutrient and pH gradient interaction between cells and the ECM 10. The real TME is composed not only of cancer cells but also of others cells such as fibroblasts, cancer-associated fibroblasts (CAFs), stromal cells, myofibroblasts, endothelial cells, adipocytes, various immune cells, and extra-abundant compromised ECM. These heterocellular components can induce adaptive survival mechanisms of cancer such as treatment resistance, a leading cause of cancer-related mortality and one of the greatest challenges in cancer treatment 11. The cellular responses and cell signaling that take place in the TME often cannot be mimicked in a 2D in vitro model.

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Quantification of cellular associated graphene and induced surface receptor responses

Abstract: The use of graphene for biomedical and other applications involving humans is growing and shows practical promise.

Cited by 10 publications

References 46 publications

<p>Functionalized Graphene Nanoparticles Induce Human Mesenchymal Stem Cells to Express Distinct Extracellular Matrix Proteins Mediating Osteogenesis</p>

<p>Functionalized Graphene Nanoparticles Induce Human Mesenchymal Stem Cells to Express Distinct Extracellular Matrix Proteins Mediating Osteogenesis</p>

Comparative Effects of Graphene and Molybdenum Disulfide on Human Macrophage Toxicity

Tracking Gold Nanorods’ Interaction with Large 3D Pancreatic-Stromal Tumor Spheroids by Multimodal Imaging: Fluorescence, Photoacoustic, and Photothermal Microscopies

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