The cellular uptake and cytotoxic effect of silver nanoparticles on chronic myeloid leukemia cells

Area of Science:

• Nanomedicine
• Cancer Biology
• Hematology

Background:

• Silver nanoparticles (AgNPs) are explored for anti-cancer properties, particularly in leukemia.
• Mechanisms of AgNP cytotoxicity and efficacy on patient-derived leukemia cells require further elucidation.

Purpose of the Study:

• To investigate the cellular uptake and cytotoxic mechanisms of AgNPs in chronic myeloid leukemia (CML) cells.
• To assess the efficacy of AgNPs on primary CML patient cells and identify potential therapeutic applications.

Main Methods:

• AgNPs synthesized via a modified polyol method, confirmed stable in cell culture with fetal bovine serum (FBS).
• Cellular uptake, localization (endosomes), reactive oxygen species (ROS) generation, cytotoxicity, apoptosis, cell cycle analysis, and gene expression in K562 cells and primary CML patient cells.
• Reversal of AgNP-induced effects using Vitamin C.

Main Results:

• AgNPs were internalized by K562 cells in a dose-dependent manner and localized within endosomes.
• AgNP exposure induced significant ROS generation, leading to cytotoxicity and apoptosis in CML cells.
• AgNP treatment reduced the viability of cells from CML patients and altered cell cycle regulators.
• AgNP-induced cellular and molecular changes were reversible with Vitamin C treatment.

Conclusions:

• AgNPs exhibit promising anti-leukemic activity against CML cells through ROS-mediated cytotoxicity and apoptosis.
• AgNPs demonstrate efficacy on primary CML patient cells, suggesting therapeutic potential.
• The effects of AgNPs are mediated by ROS and can be modulated by antioxidants like Vitamin C, guiding future CML treatment strategies.