Control of cell death by the smart polymeric vehicle

We report a novel drug delivery system for apoptosis induction by a "smart" polymer vehicle possessing thermosensitivity and bioaffinity. The polymer chain was prepared by copolymerization of N-isopropyl-acrylamide and N-methacryloyloxysuccinimide. Cell-adhesive RGDS peptide was conjugated with the copolymer as a ligand model for bioaffinity. When the temperature was increased, nanoscale aggregates precipitated from a copolymer aqueous solution. Either dolichyl phosphate (dol-p), which is an apoptotic inducer, or dolichol was added to aggregates at around the precipitation temperature (31°C), and the temperature was raised to 37°C for incorporation. Aggregates incorporating dol-p or dolicol were added to a human promonocytic leukemia U937 cell suspension at 37°C. When the temperature was lowered to 25 °C, cells underwent apoptosis in the presence of Ca²⁺. Probably, copolymer vehicles were concentrated on a cell surface through the binding of RGDS and integrin and the release of lipid inducers was caused by the disruption of vehicles in response to temperature.