Noble metal/dextran-graft-polyacrylamide branched polymer nanocomposites induce ROS-dependent apoptosis in diffuse large B-cell lymphoma cells

In general, polymer/metal nanocomposites might have better anti-cancer properties in comparison to standalone metal nanoparticles (NPs). This emerging class of functional nanomaterials shows improved and more selective tumor delivery with lower toxicity against non-tumor tissues, providing a better biocompatibility and higher effectiveness. Herein, the cytotoxicity of four two-component nanocomposites comprising a metal NP (Au or Ag) and a star-like polymer (dextran-graft-polyacrylamide, D-PAA, or its anionic form, D-PAAan) was tested against multiple diffuse large B-cell lymphoma (DLBCL) cell lines. Our findings suggest that these nanocomposites reduce the viability of DLBCL cells in a dose-dependent manner. The cytotoxic effect of the investigated two-component nanocomposites was mediated by overproduction of reactive oxygen species (ROS, especially in the case of AuNP-based nanocomposites), elevation of intracellular Fe²⁺ levels, with consequent activation of lipid peroxidation and reduced glutathione (GSH) downregulation. Unexpectedly, the nanocomposites did not trigger ferroptosis, which is a type of regulated cell death heavily dependent on ROS and Fe²⁺. Nanocomposite-induced cell death occurred via apoptosis, as evidenced by the activation of caspase-3/7. Interestingly, the tested nanocomposites induced substantial compensatory activation of the pro-survival PI3K/AKT (phosphatidylinositol 3‑kinase/protein kinase B) pathway. However, this was not sufficient to prevent nanocomposite-induced apoptosis. We have demonstrated the anti-lymphoma potential of four noble metal/polymer nanocomposites. Their cytotoxic and anti-lymphoma effects are primarily attributable to oxidative stress with consequent induction of apoptosis.