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.

• Klíčová slova
• Cell death, Glioblastoma, Gold nanorods, Plasmonic photothermal effect, Pyroptosis, Tumor spheroids,
• MeSH
• buněčné sféroidy účinky léků   patologie   MeSH
• fototermální terapie MeSH
• gliom * patologie   farmakoterapie   metabolismus   MeSH
• kationty chemie   farmakologie   MeSH
• kovové nanočástice chemie   MeSH
• kvartérní amoniové sloučeniny chemie   farmakologie   MeSH
• lidé MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nádorové buňky kultivované MeSH
• nanotrubičky * chemie   MeSH
• pyroptóza * účinky léků   MeSH
• viabilita buněk účinky léků   MeSH
• zlato * chemie   farmakologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• kationty MeSH
• kvartérní amoniové sloučeniny MeSH
• zlato * MeSH