Abstract

Recently, graphene and graphene related nanocomposite receive much attention due to high surface-to-volume ratio, and unique physiochemical and biological properties. The combination of metallic nanoparticles with graphene-based materials offers a promising method to fabricate novel graphene–silver hybrid nanomaterials with unique functions in biomedical nanotechnology, and nanomedicine. Therefore, this study was designed to prepare graphene oxide (GO) silver nanoparticles (AgNPs) nanocomposite (GO-AgNPs) containing two different nanomaterials in single platform with distinctive properties using luciferin as reducing agents. In addition, we investigated the effect of GO-AgNPs on differentiation in SH-SY5Y cells. The synthesized GO-AgNPs were characterized by ultraviolet-visible absorption spectroscopy (UV-vis), X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and Raman spectroscopy. The differentiation was confirmed by series of cellular and biochemical assays. The AgNPs were distributed uniformly on the surface of graphene oxide with an average size of 25 nm. As prepared GO-AgNPOs induces differentiation by increasing the expression of neuronal differentiation markers and decreasing the expression of stem cell markers. The results indicated that the redox biology involved the expression of various signaling molecules, which play an important role in differentiation. This study suggests that GO-AgNP nanocomposite could stimulate differentiation of SH-SY5Y cells. Furthermore, understanding the mechanisms of differentiation of neuroblastoma cells could provide new strategies for cancer and stem cell therapies. Therefore, these studies suggest that GO-AgNPs could target specific chemotherapy-resistant cells within a tumor.

Highlights

  • Neuroblastoma is the most common solid tumor of infancy and it accounts for more than 7% of childhood cancers and 15% of cancer-related childhood deaths [1]

  • Pelin et al reported that the biocompatibility of various types of graphene oxide (GO) on skin keratinocytes; the results displayed significant cellular damage induced by few-layer graphene (FLG) and GOs only at high concentrations (>0 μg/mL and >1 μg/mL for FLG and GOs, respectively) after the cells were exposed for 72 h, with variable potencies depending on graphene-based materials (GBMs) oxidation state

  • A study was performed based on dose and time in both undifferentiated and differentiated human adipose-derived stem cells cells using 10- and 20-nm AgNPs; the results revealed that no significant viability loss was observed in undifferentiated hASC

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Summary

Introduction

Neuroblastoma is the most common solid tumor of infancy and it accounts for more than 7% of childhood cancers and 15% of cancer-related childhood deaths [1]. Neuroblastoma is an embryonic malignancy of early childhood originating from neural crest cells and it is most common extracranial solid tumor that arises from the developing sympathetic nervous system occurring in childhood with different clinical presentation [2,3]. Previous studies reported that tumor regression is induced by several factors including nutrient conditions, chemicals, and genetic processes by the process of cancer cells into normal cells by the process of differentiation [8,9]. The significance of differentiation of cancer cells into normal tissue cells, which contributes to tumor regression, is induced by some factors, including genetic processes, nutrient conditions, and chemicals [13]. Substrates coated with AgNPs, serving as favorable anchoring sites, significantly enhance neurite outgrowth [15] These studies suggest that restoration of normal function or differentiated phenotypes in cancer cells are related to tumor suppressive function. CCoonnssiiddeerriinngg tthhee lliitteerraattuurree,, wwee ddeessiiggnneedd tthhee ffoolllloowwiinngg oobbjjeeccttiivveess:: ((11)) ssyynntthheessiiss aanndd cchhaarraacctteerriizzaattiioonn ooff ggrraapphheennee ooxxiiddee––ssiillvveerr nnaannooppaarrttiiccllee nnaannooccoommppoossiitteessuussiinngglulucicfiefreirninasarsedreudcuincginagndansdtabstialibziilnizginaggeangt;e(n2t);e(v2a)luevatailounaotifotnheopf othteentpioalteenffteiactl oefffebcitoomfoblieocmuloeleacsusliestaesdsigstreadphgeranpehoexniedeo–xsidilev–esrilnvaenr onpaanrotpicalertincalennocaonmocpoomsipteossiotens odniffdeirfefenrteianttiioantioinn hinuhmuamn anneunreoubrloabstloasmtoamcaanccaenrcceerllcse(lSlsH(-SSHY-5SYY)5uYs)inugsibnagttberaitetseroifesceolfluclealrlualnadr abniodchbeiomchiceaml aicssaalyass;saanyds; (a3n)din(3v)eisntivgeasttiiognatioofntohfethmeemcheacnhiasnmismof oifnidnudcuticotnionofofddififfefererenntitaiatitoionnuuisisnngg ggrraapphheennee ooxxiiddee––ssiillvveerr nnaannooppaarrttiiccllee nnaannooccoommppoossiitteess bbyy aannaallyyssiiss ooff eexxpprreessssiioonn ooff ggeenneess iinnvvoollvveedd iinn ddiiffffeerreennttiiaattiioonn

Synthesis and Characterization of GO and GO-AgNPs Using Luciferin
GO-AgNPs Increase the Expression Level of Neuronal Markers in SH-SY5Y Cells
Materials
Synthesis of GO
Synthesis of AgNPs
Synthesis and Characterization of GO-AgNPs Nanocomposite
Cell Culture and Exposure of SH-SY5Y Cells to GO-AgNPs Nanocomposite
Cell Viability Assay
Cell Proliferation Assay
BrdU Cell Proliferation Assay
3.10. Measurement of Oxidative and Anti-Oxidative Stress Markers
3.12. Statistical Analyses
Findings
Conclusions
Full Text
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