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-isopropylacrylamide and N-metha cryloyloxysuccinimide. Cell-adhesive RGDS peptide was conjugated with the c opolymer as a ligand model for bioaffinity. When the temperature was increa sed, nanoscale aggregates precipitated from a copolymer aqueous solution. E ither dolichyl phosphate (dol-p), which is an apoptotic inducer, or dolicho l was added to aggregates at around the precipitation temperature (31 degre esC), and the temperature was raised to 37 degreesC for incorporation. Aggr egates incorporating dol-p or dolicol were added to a human promonocytic le ukemia U937 cell suspension at 37 degreesC. When the temperature was lowere d to 25 degreesC, cells underwent apoptosis in the presence of Ca2+. Probab ly, copolymer vehicles were concentrated on a cell surface through the bind ing of RGDS and integrin and the release of lipid inducers was caused by th e disruption of vehicles in response to temperature.