Citrate-Stabilized Gold Nanorods-Directed Osteogenic Differentiation of Multiple Cells

Int J Nanomedicine. 2021 Apr 12:16:2789-2801. doi: 10.2147/IJN.S299515. eCollection 2021.

Abstract

Objective: Gold nanorods (AuNRs) show great potential for versatile biomedical applications, such as stem cell therapy and bone tissue engineering. However, as an indispensable shape-directing agent for the growth of AuNRs, cetyltrimethylammonium bromide (CTAB) is not optimal for biological studies because it forms a cytotoxic bilayer on the AuNR surface, which interferes with the interactions with biological cells.

Methods: Citrate-stabilized AuNRs with various aspect-ratios (Cit-NRI, Cit-NRII, and Cit-NRIII) were prepared by the combination of end-selective etching and poly(sodium 4-styrenesulfonate)-assisted ligand exchange method. Their effects on osteogenic differentiation of the pre-osteoblastic cell line (MC3T3-E1), rat bone marrow mesenchymal stem cells (rBMSCs), and human periodontal ligament progenitor cells (PDLPs) have been investigated. Potential signaling pathway of citrate-stabilized AuNRs-induced osteogenic effects was also investigated.

Results: The experimental results showed that citrate-stabilized AuNRs have superior biocompatibility and undergo aspect-ratio-dependent osteogenic differentiation via expression of osteogenic marker genes, alkaline phosphatase (ALP) activity and formation of mineralized nodule. Furthermore, Wnt/β-catenin signaling pathway might provide a potential explanation for the citrate-stabilized AuNRs-mediated osteogenic differentiation.

Conclusion: These findings revealed that citrate-stabilized AuNRs with great biocompatibility could regulate the osteogenic differentiation of multiple cell types through Wnt/β-catenin signaling pathway, which promote innovative AuNRs in the field of tissue engineering and other biomedical applications.

Keywords: Wnt/β-catenin signaling pathway; citrate-stabilized; gold nanorods; multiple cells; osteogenic differentiation.

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Animals
  • Calcification, Physiologic / drug effects
  • Cell Differentiation / drug effects*
  • Cells, Cultured
  • Cetrimonium / pharmacology
  • Citric Acid / pharmacology*
  • Endocytosis / drug effects
  • Gene Expression Regulation / drug effects
  • Gold / pharmacology*
  • Humans
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects
  • Mice
  • Nanotubes / chemistry*
  • Nanotubes / ultrastructure
  • Osteogenesis / drug effects*
  • Osteogenesis / genetics
  • Periodontal Ligament / cytology
  • Rats
  • Thiazolidines / pharmacology
  • Wnt Signaling Pathway / drug effects

Substances

  • KYA1797K
  • Thiazolidines
  • Citric Acid
  • Gold
  • Alkaline Phosphatase
  • Cetrimonium

Grants and funding

This work was supported by National Natural Science Foundation of China (81802135, 81972124, 81730067, and 81420108021), the Natural Science Foundation of Jiangsu Province (Nos. BK20200121 and\, 20170123), Nanjing University Innovation Program for PhD candidate (CXYJ21-62), Key project in Medical science and Technology Development of Nanjing (ZKS18020), National Key Research and Development Project (Grant No. 2018YFF0301100) and 789 Outstanding Talent Program of SAHNMU.