Ag/Au Bimetallic Nanoparticles Trigger Different Cell Death Pathways and Affect Damage Associated Molecular Pattern...

Area of Science:

• Nanotechnology
• Cancer Biology
• Immunology

Background:

• Apoptosis is a standard cancer therapy, but resistance necessitates alternative cell death pathways.
• Pyroptosis and necroptosis offer alternative cell death routes.
• Damaged cancer cells release danger signals (HMGB1, HSP70) that enhance anti-tumor immunity.

Purpose of the Study:

• Investigate the cytotoxic effects of silver-gold nanoparticles (AgAu NPs), silver nanoparticles (Ag NPs), and gold nanoparticles (Au NPs).
• Determine the impact on programmed cell death (apoptosis, necroptosis, pyroptosis).
• Assess the release of high-mobility group box 1 (HMGB1) and heat shock protein 70 (HSP70).

Main Methods:

• Cancer cell lines incubated with varying concentrations of AgAu NPs, Ag NPs, and Au NPs.
• Cytotoxicity assessed via MTS assay.
• Programmed cell death and immune response genes analyzed using mRNA fold change (CASP1, CASP3, BCL-2, ZBP1, HMGB1, HSP70, CXCL8, CSF1, CCL20, NLRP3, IL-1β, IL-18).
• Extracellular HMGB1 and IL-1β levels quantified using ELISA.

Main Results:

• Nanoparticles exhibited dose-dependent toxicity.
• Pyroptosis induced in LNCaP and MDA-MB-231 cells; necroptosis in MDA-MB-231 cells.
• HCT116 cells underwent apoptosis with increased extracellular HMGB1.
• AgAu NPs induced mixed programmed cell death in P53-deficient MDA-MB-231 cells.
• IL-1β release observed in MDA-MB-231 and LNCaP cells; HMGB1 release in HCT116 cells.

Conclusions:

• AgAu NPs trigger diverse programmed cell death mechanisms dependent on the cellular microenvironment.
• Nanoparticle-induced cell death pathways and danger signal release present therapeutic potential.
• Further research into nanoparticle-mediated immunogenic cell death is warranted.