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

Hector Katifelis1, Maria-Paraskevi Nikou1, Iuliia Mukha2

  • 1Laboratory of Biology, Department of Basic Medical Sciences, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece.

Cancers
|March 25, 2022
PubMed

Insights

Silver-gold nanoparticles induce distinct programmed cell death pathways like pyroptosis and necroptosis in cancer cells. These nanoparticles also trigger the release of danger signals, potentially enhancing antitumor immunity.

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.
Keywords:
apoptosisbimetallic nanoparticlesgoldnecroptosispyroptosissilver

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