Thermally triggered intracellular explosion of volume transition nanogels for necrotic cell death

Here we report a novel class of super-expandable smart nanogels that undergo nano- to micro-scale volume transition in response to temperature change, applicable for thermally triggered death of cancer cells. The nanogels fabricated by light cross-linking between oligo(l-lactic acid)-poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide)-oligo(l-lactic acid) and poly(ethylene glycol) grafted poly(l-lysine) exhibited a reversible volume transition from ~ 150 nm at 37 °C to ~ 1.4 μm at 15 °C. The abrupt and dramatic intracellular volume expansion of the nanogels upon the brief cold-shock treatment severely damaged sub-cellular self-assembled network architectures including cytoskeleton and vesicular membranes and physically ruptured cellular membrane structures, resulting in necrotic cell death. The smart "nanobomb" detonated by external stimuli could be used to effectively induce traumatic death of cells.