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

Zhang, Yixun; Lin, Jundong; Zhuo, Yangjia; Zou, Zhihao; Li, Yuejiao; Yang, Huiting; Xie, Wenjie; Zeng, Jie; Deng, Yulin; Cai, Shanghua; Ye, Jian‐Heng; Fen, Zou; Zhong, Weijie

doi:10.1016/j.bioadv.2022.212745

Cited by 7 publications

(3 citation statements)

References 41 publications

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“…Xu et al [ 92 ] also reported alterations in the glycine, serine, and threonine metabolism pathways after the 24-h-treatment of TM-4 mouse Sertoli cells with AuNPs (rods, 10 nm width, 40 nm length), corroborating the idea of a general panel of biological pathways associated with AuNPs toxicity [ 92 ]. Recently, untargeted metabolomics experiments revealed that 80 nm double-stranded DNA-modified AuNPs (AuNPs-dsDNA) can possibly regulate the metabolic reprogramming of PC3 and DU145 prostate cancer cell lines mainly through the lipid metabolic pathways [ 93 ]. Since metabolic reprogramming plays an important role in the development of prostate cancer, this result provides an important basis for future research on the characteristic targeted design of nanomaterials for cancer metabolism [ 93 ].…”

Section: Insights Into the Molecular Effects Of Aunps In Biological S...mentioning

confidence: 99%

“…Recently, untargeted metabolomics experiments revealed that 80 nm double-stranded DNA-modified AuNPs (AuNPs-dsDNA) can possibly regulate the metabolic reprogramming of PC3 and DU145 prostate cancer cell lines mainly through the lipid metabolic pathways [ 93 ]. Since metabolic reprogramming plays an important role in the development of prostate cancer, this result provides an important basis for future research on the characteristic targeted design of nanomaterials for cancer metabolism [ 93 ]. The metabolomics changes caused by cells exposure to AuNPs are shown in Table 4 .…”

Section: Insights Into the Molecular Effects Of Aunps In Biological S...mentioning

confidence: 99%

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Mechanistic Insights into the Biological Effects of Engineered Nanomaterials: A Focus on Gold Nanoparticles

Nguyen

Falagan-Lotsch

2023

IJMS

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Nanotechnology has great potential to significantly advance the biomedical field for the benefit of human health. However, the limited understanding of nano–bio interactions leading to unknowns about the potential adverse health effects of engineered nanomaterials and to the poor efficacy of nanomedicines has hindered their use and commercialization. This is well evidenced considering gold nanoparticles, one of the most promising nanomaterials for biomedical applications. Thus, a fundamental understanding of nano–bio interactions is of interest to nanotoxicology and nanomedicine, enabling the development of safe-by-design nanomaterials and improving the efficacy of nanomedicines. In this review, we introduce the advanced approaches currently applied in nano–bio interaction studies—omics and systems toxicology—to provide insights into the biological effects of nanomaterials at the molecular level. We highlight the use of omics and systems toxicology studies focusing on the assessment of the mechanisms underlying the in vitro biological responses to gold nanoparticles. First, the great potential of gold-based nanoplatforms to improve healthcare along with the main challenges for their clinical translation are presented. We then discuss the current limitations in the translation of omics data to support risk assessment of engineered nanomaterials.

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Section: Insights Into the Molecular Effects Of Aunps In Biological S...mentioning

confidence: 99%

Section: Insights Into the Molecular Effects Of Aunps In Biological S...mentioning

confidence: 99%

Mechanistic Insights into the Biological Effects of Engineered Nanomaterials: A Focus on Gold Nanoparticles

Nguyen

Falagan-Lotsch

2023

IJMS

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“…Cellular metabolomics is a very important field in systems biology because it reflects the cell phenotype and monitors cellular activity within a disturbed system [21]. Untargeted metabolomics is the analysis of a large number of detected metabolites to screen for biologically significant and statistically significant differential metabolites and to elucidate related metabolic processes and mechanistic changes [22]. In this study, MDA-MB-231 cells were compared with a blank control group after treatment with pH-responsive GA micelles for metabolomic analysis.…”

Section: Metabolomicsmentioning

confidence: 99%

Therapeutic effect and metabolic fingerprinting of triple-negative breast cancer cells following exposure to a novel pH-responsive, gambogic acid-loaded micelle

Da,

Li,

Yang

et al. 2023

Nanotechnology

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Triple-negative breast cancer (TNBC) is a subtype of breast cancer with a poor prognosis and lacks effective therapeutic targets. The use of gambogic acid (GA), a class of active ingredients in traditional Chinese medicine with anti-tumour potential, is limited in tumour therapy owing to its drawbacks and unclear organ toxicity. In this study, we used the pH-responsive amphiphilic block copolymer, PEOz-PCL, to create nanodrugs for GA delivery to MDA-MB-231 cells. The pH-responsive GA-loaded micelles were prepared through nanoprecipitation with a more homogeneous size. The average particle size was 42.29 ± 1.74 nm, and the zeta potential value was 9.88 ± 0.17 mV. The encapsulation rate was 85.06%, and the drug loading rate was 10.63%. The process was reproducible, and sustained release reached 80% in 96 h at acid pH 5.0. Furthermore, cellular tests using CCK-8, TUNEL, and flow cytometry revealed that pH-responsive GA-loaded micelles killed MDA-MB-231 cells more effectively and had much higher activity and targeting compared with free drugs. Metabolomic analysis of the changes in differential metabolites revealed that pH-responsive GA-loaded micelles may inhibit TNBC cells by causing amino acid anabolism, nucleotide metabolism, and glucose metabolism, as well as by affecting their energy sources. The study outcomes will help understand the mechanism of action and the therapeutic efficacy of pH-responsive GA-loaded micelles in vivo.

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Intravenous administration of gold nanoparticles in rats exhibit alterations in sphingomyelins, bile acids, sphingolipids, and cholesterol esters levels

Al-Sulaiti,

Ismail,

Anwardeen

et al. 2024

emergent mater.

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Nanoparticles (NP) have gained significant attention in biomedical research due to their unique properties and potential applications in drug delivery, imaging, and diagnostics. Gold (AuNPs) and silver (AgNPs) NPs are among the important nanoplatforms that received extensive attention recently for various biomedical applications. Understanding the complex interaction of these NP in biological systems is essential to unveil their pharmacological, Pharmacokinetic and toxicological attributes. Metabolomics has proven invaluable in providing detailed insights into NP’s biodistribution, metabolic effects, and potential toxicity. This study aims to investigate the underlying metabolic pathways affected by in vivo exposure to NP using a robust metabolomics approach. In this work, spherical polyethylene glycol (PEG) modified AuNPs (13 nm, diameter) or AgNPs (20 nm, diameter) were synthesized and dosed into rats via intravenous route to study the associated metabolic changes. Rats (n = 14) were divided into three groups: control (n = 2), AuNPs (n = 6) and AgNPs (n = 6), to mimic potential biomedical exposure scenarios. Duplicate serum samples were collected 24 h post-dosing, and comprehensive metabolite profiling was performed using liquid chromatography-mass spectrometry (LC-MS/MS) and flow injection analysis-mass spectrometry (FIA-MS/MS). Metabolite extraction followed the MxP Quant 500 Kit protocol, with chromatographic separation using the Xevo TQS system. Metabolite identification and quantification were conducted with isotopically labelled internal standards and multiple reaction monitoring (MRM), utilizing optimized conditions under mass spectrometry (MS) as provided by Biocrates. Annotation of metabolites was determined by retention times and specific MRMs for each compound. Results indicate that AuNPs treatment significantly impacted several metabolic pathways. Notably, there was an increase in sphingomyelin (SM 34:2) levels (estimate 0.23, p ≤ 0.001), which are critical for cell membrane structure and signalling. Additionally, a decrease in glycochenodeoxycholic acid levels was also triggered by treatment with AuNPs, suggesting modulation of bile acid metabolism with potential effects on lipid homeostasis. Furthermore, treatment with AuNPs caused significant alterations in cholesterol ester levels, essential for lipid storage and transport, indicating disruptions in these mechanisms. These metabolic changes suggest that gold nanoparticles can disrupt fatty acid metabolism, pyrimidine/purine metabolism, and amino acid synthesis. These findings contribute to the growing understanding of nanoparticle toxicity profile and underscore the need for further research to ensure the safe application of nanoparticles in biomedical and other fields.

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

Cited by 7 publications

References 41 publications

Mechanistic Insights into the Biological Effects of Engineered Nanomaterials: A Focus on Gold Nanoparticles

Mechanistic Insights into the Biological Effects of Engineered Nanomaterials: A Focus on Gold Nanoparticles

Therapeutic effect and metabolic fingerprinting of triple-negative breast cancer cells following exposure to a novel pH-responsive, gambogic acid-loaded micelle

Intravenous administration of gold nanoparticles in rats exhibit alterations in sphingomyelins, bile acids, sphingolipids, and cholesterol esters levels

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