Selenium nanoparticles decorated by fucoidan induce ferroptosis in HepG2 cells

Area of Science:

• Biochemistry
• Cell Biology
• Nanomedicine

Background:

• Ferroptosis is a novel regulated cell death distinct from apoptosis, necrosis, and autophagy.
• The mechanism of selenium nanoparticles inducing ferroptosis in cancer cells remains underexplored.

Purpose of the Study:

• To investigate how fucoidan-selenium nanoparticles (FD-SeNPs) inhibit HepG2 cell proliferation by inducing ferroptosis.
• To elucidate the molecular mechanisms underlying FD-SeNP-induced ferroptosis.

Main Methods:

• Detection of reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), and Fe2+ levels.
• Transmission electron microscopy (TEM) and Western blot assays.
• Intervention with Ferrostatin-1 (Fer-1) to validate ferroptosis induction.

Main Results:

• FD-SeNPs increased intracellular ROS, MDA, and Fe2+ levels, while decreasing GSH levels.
• TEM revealed mitochondrial shrinkage, volume reduction, and cristae breakage in HepG2 cells.
• FD-SeNPs modulated proteins involved in lipid peroxidation (Nrf2, HO-1, SLC7A11, GCLC, GPX4) and iron homeostasis (transferrin, SLC40A1, Ferritin).

Conclusions:

• FD-SeNPs inhibit HepG2 cell proliferation by inducing ferroptosis, confirmed by Fer-1 intervention.
• FD-SeNPs promote lipid peroxidation and disrupt iron homeostasis, key mechanisms in ferroptosis induction.
• This study provides a theoretical basis for developing FD-SeNPs as anti-cancer clinical drugs.