Untargeted metabolomics reveals alterations in the metabolic reprogramming of prostate cancer cells by double-stranded DNA-modified gold nanoparticles

Yixun Zhang; Jundong Lin; Yangjia Zhuo; Zhihao Zou; Yuejiao Li; Huikang Yang; Wenjie Xie; Jie Zeng; Yulin Deng; Shanghua Cai; Jianheng Ye; Fen Zou; Weide Zhong

doi:10.1016/j.bioadv.2022.212745

Untargeted metabolomics reveals alterations in the metabolic reprogramming of prostate cancer cells by double-stranded DNA-modified gold nanoparticles

Biomater Adv. 2022 Apr:135:212745. doi: 10.1016/j.bioadv.2022.212745. Epub 2022 Mar 18.

Authors

Yixun Zhang¹, Jundong Lin¹, Yangjia Zhuo¹, Zhihao Zou¹, Yuejiao Li², Huikang Yang², Wenjie Xie¹, Jie Zeng¹, Yulin Deng¹, Shanghua Cai¹, Jianheng Ye¹, Fen Zou³, Weide Zhong⁴

Affiliations

¹ Department of Urology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China.
² Department of Urology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China; Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China.
³ Department of Urology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China. Electronic address: zoufen2008@126.com.
⁴ Department of Urology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China. Electronic address: zhongwd2009@live.cn.

PMID: 35929217
DOI: 10.1016/j.bioadv.2022.212745

Abstract

Metabolic reprogramming plays an important role in the development of prostate cancer (PCa). However, there are few reports on the effects of nanomaterials as vectors on cancer metabolic reprogramming. Herein, a type of nanoparticle with good biocompatibility was synthesized by modifying the double-stranded of DNA containing a sulfhydryl group on the surface of gold nanoparticles (AuNPs-dsDNA) through salt-aging conjugation methods. The resultant AuNPs-dsDNA complexes possessed low toxicity to PC3 and DU145 cells in vitro. There was also no obvious hepatorenal toxicity after intravenous injection of AuNPs-dsDNA complexes in vivo, which indicated that these nanoparticles had good biological compatibilities. We investigated their biological functions using prostate cancer cells. Seahorse assay showed that AuNPs-dsDNA complexes could increase glycolysis and glycolysis capacity both in PC3 and DU145 cells. We further detected the expression of glycolysis-related genes by qPCR assay, and found that PKM2, PDHA, and LDHA were significantly upregulated. Furthermore, untargeted metabolomics revealed that PC (18:2(9Z,12Z)/18:2(9Z,12Z)) and PC (18:0/18:2 (9Z,12Z)) levels were decreased and inosinic acid level was increased in PC3 cells. Whereas (3S,6E,10E)-1,6,10,14-Phytatetraen-3-ol, Plasmenyl-PE 36:5 and Cer (d18:2/18:2) were decreased, PE 21:3 and 1-pyrrolidinecarboxaldehyde were increased in DU145 cells after co-culturing with AuNPs-dsDNA. In summary, we found that AuNPs and AuNPs-dsDNA complexes possibly regulate the metabolic reprogramming of cancer cells mainly through the lipid metabolic pathways, which could compensate for the previously mentioned phenomenon of enhanced glycolysis and glycolysis capacity. This will provide an important theoretical basis for our future research on the characteristic targeted design of nanomaterials for cancer metabolism.

Keywords: Double-stranded DNA-modified gold nanoparticles; Metabolic reprogramming; Prostate cancer; Untargeted metabolomics.

MeSH terms

DNA / analysis
Gold / metabolism
Humans
Male
Metal Nanoparticles* / toxicity
Prostate / chemistry
Prostatic Neoplasms* / genetics

Substances

Gold
DNA