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 approximately 150 nm at 37 degrees C to approximately 1.4 microm at 15 degrees 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.
Lee
Yuhan
Y
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
Park
Sung Young
SY
Kim
Chunsoo
C
Park
Tae Gwan
TG
D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D016650:Fluorescein-5-isothiocyanate; D006367:HeLa Cells; D006801:Humans; D020100:Hydrogels / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D000080385:Nanogels; D009336:Necrosis; D010316:Particle Size; D044367:Phase Transition; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011094:Polyethyleneimine / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011107:Polylysine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D013499:Surface Properties; D013696:Temperature
D004337:Drug Carriers; D020100:Hydrogels; D000080385:Nanogels; D011091:Polyesters; C542500:oligo(lactic acid)-b-pluronic F127-b-oligo(lactic acid); C413692:polyethylene glycol polyethyleneimine nanogel; C443714:polylysine-graft-(poly(ethylene glycol)); D011107:Polylysine; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D016650:Fluorescein-5-isothiocyanate