Hyaluronic acid/kaempferol-functionalized FeO nanoparticles promote ROS-associated apoptosis and modulate

Deniz Kazemzadeh1, Ali Salehzadeh2, Shahab Shariati3

  • 1Department of Biology, Ra.C., Islamic Azad University, Rasht, Iran.

Scientific Reports
|May 12, 2026
PubMed

Insights

Novel iron oxide nanoparticles functionalized with glucose, hyaluronic acid (HA), and Kaempferol (KAE) show potent anticancer effects against triple-negative breast cancer (TNBC). These nanoparticles induce apoptosis and cell cycle arrest, offering a promising new strategy for TNBC treatment.

Area of Science:

  • Biomedical Nanotechnology
  • Cancer Therapeutics
  • Materials Science

Background:

  • Triple-negative breast cancer (TNBC) remains a challenging subtype with limited targeted therapies.
  • Hyaluronic acid receptor targeting presents an innovative strategy for drug delivery and cancer treatment.
  • Iron oxide nanoparticles offer versatile platforms for therapeutic applications.

Purpose of the Study:

  • To synthesize and characterize novel Fe3O4 nanoparticles co-conjugated with glucose, hyaluronic acid (HA), and Kaempferol (KAE) (Fe3O4@Glu-HA-KAE NPs).
  • To evaluate the anticancer properties of these NPs against TNBC cells (MDA-MB-231).
  • To investigate the underlying mechanisms of NP-induced cytotoxicity, including apoptosis and cell cycle modulation.

Main Methods:

  • Nanoparticle synthesis and characterization using FT-IR, XRD, EDS, SEM, TEM, DLS, and zeta potential.
  • Cytotoxicity assessment via MTT assays.
  • Apoptosis and cell cycle analysis using flow cytometry and AO/PI staining.
  • Reactive oxygen species (ROS) production measurement.
  • Caspase-8 expression and BCRT1 lncRNA transcript level analysis.

Main Results:

  • Fe3O4@Glu-HA-KAE NPs were successfully synthesized with a size range of 10-60 nm (dried) and 276 nm (hydrodynamic diameter).
  • The NPs demonstrated dose- and time-dependent cytotoxicity against TNBC cells, with IC50 values of 215 µg/mL (24h) and 149 µg/mL (48h).
  • Treatment induced cell cycle arrest at the sub-G1 phase, increased apoptosis to 65.1-68.1%, enhanced ROS generation, and triggered significant nuclear alterations.
  • Apoptosis was further confirmed by increased Caspase-8 expression and decreased BCRT1 lncRNA levels.

Conclusions:

  • Fe3O4@Glu-HA-KAE NPs exhibit significant anticancer efficacy against TNBC cells.
  • The nanoparticles induce cell death through apoptosis and cell cycle arrest.
  • This study highlights the potential of HA-targeted, functionalized iron oxide nanoparticles as an innovative therapeutic approach for TNBC.