Death Pathways of Cancer Cells Modulated by Surface Molecule Density on Gold Nanorods

Abstract Necrosis induces strong inflammation with undesirable implications in clinics compared with apoptosis. Fortunately, the switch between necrosis and apoptosis could be realized by tailoring the appropriate structural properties of gold nano rods (GNRs) that could precisely modulate cell death pathways. Herein, the intracellular interaction between GNRs and organelles is monitored and it is found that lysosomes dominates necrosis/apoptosis evoking. Then the surface molecule density of GNRs, which is first defined as ρ _{surf. molecule} ( N _{surf. molecules} /( a × π × Diameter × Length)), mediates lysosome activities as the membrane permeabilization (LMP), the Cathepsin B and D release, the cross‐talk between lysosome and different organelles, which selectively evokes apoptosis or necrosis and the production of TNF‐ α from macrophages. GNRs with small ρ _{surf. molecule} mainly induce apoptosis, while with large ρ _{surf. molecule} they greatly contribute to necrosis. Interestingly, necrosis can be suppressed by GNRs with higher ρ _{surf. molecule} due to the overexpression of key protease caspase 8, which cleaves the RIP1‐RIP3 complex and activates caspase 3 followed by necrosis to apoptosis transition. This investigation indicates that the ρ _{surf. molecule} greatly affects the utility of nanomaterials and different structural properties of nanomaterials have different implications in clinics.