Effects of surface-modified gold nanoparticles on cell viability and osteogenic differentiation

Abstract

Researches regarding application of nanoparticles (NPs) had unique physical and chemical characteristics in biomedical fields such as drug delivery, targeting specific cancer cell, and tissue regeneration have been progressed. In case of AuNPs known to be less toxic than other NPs, a colloidal form of AuNPs dispersed in liquid are widely used. Thus, AuNPs are synthesized with stabilizer to prevent electrochemical instability of AuNPs. AuNPs modified with stabilizer are applied in drug delivery system and diagnostic tools due to stability and easy combination with antibody. Moreover, AuNPs are investigated as therapeutic tools to stimulate differentiation of adult stem cells in tissue regeneration. However, the toxicity of AuNPs for cells according to the size, shape, and surface charge has been reported. Moreover, it is reported that the physiological and biological effects of AuNPs on cells are cell type dependent. In this study, cytotoxicity of AuNPs stabilized with citrate- and chitosan on human lung cancer cells were measured and the change of microRNA expression by exposure of AuNPs stabilized with citrate- and chitosan was predicted. Furthermore, the promoting effect of AuNPs stabilized with chitosan on osteogenic differentiation of human adipose-derived mesenchymal stem cells (hADSCs) was investigated. The results of this study revealed that differently charged AuNPs which were modified with citrate and chitosan showed toxicity in human lung cancer cells in dose-dependent manners through apoptosis and necrosis. Moreover, the expression of microRNAs that were regarded as post-transcriptional regulators was altered by exposure to citrate- and chitosan-AuNPs in human lung cancer cells. The microRNAs up-regulated by citrate-AuNPs were related to migration and metastasis. The microRNAs up-regulated by chitosan-AuNPs were related to cell proliferation, apoptosis, and differentiaton. In addition, the microRNAs down-regulated by chitosan-AuNPs were related to proliferation, apoptosis, and development signaling pathway. In a study regarding cell differentiation, chitosan-AuNPs at the concentration that does not decrease cell viability stimulate the osteogenic differentiation of hADSCs through the activation of the Wnt/β-catenin signaling pathway. Therefore, results in this study suggest that AuNPs stabilized with citrate- and chitosan should be applied as therapeutic tools for regeneration of damaged tissue, and evaluating cytotoxicity of citrate- and chitosan-AuNPs should be estimated prior to biomedical application. This study focuses on (1) the cytotoxic effect of citrate- and chitosan-AuNPs (Chapter I and II)

(2) alteration in the expression of microRNAs by citrate- and chitosan-AuNPs (Chapter III) in human lung cancer cells

and (3) the promotion of osteogenic differentiation of hADSCs by chitosan-AuNPs (Chapter IV).