Gold nanoparticles regulate the antitumor secretome and have potent cytotoxic effects against prostate cancer cells

• Published in: Journal of applied toxicology 2021-08, Vol.41 (8), p.1286-1303
• Main Authors: Hao, Yuanyuan, Hu, Jinghai, Wang, Hao, Wang, Chunxi
• Format: Article
• Language: English
• Subjects: Cell Line, Tumor; Chemokines; Cytokines; Cytotoxicity; Cytotoxins - therapeutic use; Diffraction patterns; Electron diffraction; Electron microscopy; Electrophoresis; Electrophoresis, Gel, Two-Dimensional; Field emission microscopy; Gel electrophoresis; Gelatinase B; Gold; gold nanoparticles; Humans; Interleukins; Male; Matrix metalloproteinase; matrix metalloproteinase 9; Matrix metalloproteinases; Metal Nanoparticles - therapeutic use; Metal Nanoparticles - ultrastructure; Metalloproteinase; Microscopy; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission; Monocyte chemoattractant protein 1; Nanoparticles; Photoelectron Spectroscopy; Photoelectrons; Polymerase chain reaction; Prostate cancer; Prostatic Neoplasms - drug therapy; RNA-directed DNA polymerase; Scanning electron microscopy; Secretome; Secretome - drug effects; Spectrophotometry, Atomic; Synthesis; Transmission electron microscopy; Tumor cells; two‐dimensional difference in‐gel electrophoresis
• ISSN: 0260-437X; 1099-1263
• DOI: 10.1002/jat.4117

The specific cytotoxic effects of nanoparticles on tumor cells may be used in future antitumor clinical applications. Gold nanoparticles (AuNPs) have been reported to produce potent cytotoxic effects; however, the precise mechanism is unclear. In this study, AuNPs were synthesized; the average size of the particles was 62.2 ± 6 nm with smooth surface and multiple shapes, which were determined using transmission electron microscopy and field emission scanning electron microscopy. The selected area electron diffraction patterns suggested that the synthesized AuNPs were crystalline. The X‐ray photoelectron spectroscopy (XPS) spectrum of the synthesized AuNPs has presented an intense peak at 100 eV, signifying the entire composition of Au in the developed AuNPs. This synthesized AuNPs showed the most potent efficacy in prostate cancer cells, regardless of whether or not they were androgen dependent. Secretome determinations using two‐dimensional difference in‐gel electrophoresis (2D‐DIGE), followed by enzyme‐linked immunosorbent assay and quantitative reverse transcriptase–polymerase chain reaction validations, have identified a series of secretory proteins that were dysregulated by AuNP treatment in prostate cancer cells, many of which are highly involved in cytokine–chemokine functions, including CXCL3, interleukin‐10, CCL2, and matrix metalloproteinase 9 (MMP9). Further research on molecular mechanism has indicated that AuNPs can trigger the secretion of anticancer factors and myeloid cell‐polarizing factors from tumor cells through MMP9 inhibition. These results have clearly signified the cytotoxic potential of AuNPs for treating prostate cancer and may provide a novel direction for prostate cancer therapy in the future. We have synthesized new gold nanoparticles (AuNPs) and identified their shape, properties, and components. This type of AuNPs has demonstrated significant cytotoxicity on prostate cancer cells, and they can regulate the polarization of myeloid cells in the tumor microenvironment. A series of secretory proteins regulated by AuNPs were screened using a proteomic method; and a secretory protein, matrix metalloproteinase 9, was proven to mediate the function of AuNPs on prostate cancer cells.