Photothermal induction of pyroptosis in malignant glioma spheroids using (16-mercaptohexadecyl)trimethylammonium bromide-modified cationic gold nanorods
Language English Country Netherlands Media print-electronic
Document type Journal Article
PubMed
39094210
DOI
10.1016/j.colsurfb.2024.114128
PII: S0927-7765(24)00387-4
Knihovny.cz E-resources
- Keywords
- Cell death, Glioblastoma, Gold nanorods, Plasmonic photothermal effect, Pyroptosis, Tumor spheroids,
- MeSH
- Spheroids, Cellular drug effects pathology MeSH
- Photothermal Therapy MeSH
- Glioma * pathology drug therapy metabolism MeSH
- Cations chemistry pharmacology MeSH
- Metal Nanoparticles chemistry MeSH
- Quaternary Ammonium Compounds chemistry pharmacology MeSH
- Humans MeSH
- Mice MeSH
- Cell Line, Tumor MeSH
- Tumor Cells, Cultured MeSH
- Nanotubes * chemistry MeSH
- Pyroptosis * drug effects MeSH
- Cell Survival drug effects MeSH
- Gold * chemistry pharmacology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Cations MeSH
- Quaternary Ammonium Compounds MeSH
- Gold * MeSH
Plasmonic photothermal therapy (PPTT) employing plasmonic gold nanorods (GNRs) presents a potent strategy for eradication of tumors including aggressive brain gliomas. Despite its promise, there is a pressing need for a more comprehensive evaluation of PPTT using sophisticated in vitro models that closely resemble tumor tissues, thereby facilitating the elucidation of therapeutic mechanisms. In this study, we exposed 3D glioma spheroids (tumoroids) to (16-mercaptohexadecyl)trimethylammonium bromide-functionalized gold nanorods (MTAB-GNRs) and a near-infrared (NIR) laser. We demonstrate that the photothermal effect can be fine-tuned by adjusting the nanoparticle concentration and laser power. Depending on the selected parameters, the laser can trigger either regulated or non-regulated cell death (necrosis) in both mouse GL261 and human U-87 MG glioma cell lines, accompanied by translocation of phosphatidylserine in the membrane. Our investigation into the mechanism of regulated cell death induced by PPTT revealed an absence of markers associated with classical apoptosis pathways, such as cleaved caspase 3. Instead, we observed the presence of cleaved caspase 1, gasdermin D, and elevated levels of NLRP3 in NIR-irradiated tumoroids, indicating the activation of pyroptosis. This finding correlates with previous observations of lysosomal accumulation of MTAB-GNRs and the known lysosomal pathway of pyroptosis activation. We further confirmed the absence of toxic breakdown products of GNRs using electron microscopy, which showed no melting or fragmentation of gold nanoparticles under the conditions causing regulated cell death. In conclusion, PPTT using coated gold nanorods offers significant potential for glioma cell elimination occurring through the activation of pyroptosis rather than classical apoptosis pathways.
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