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-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 degrees C), and the temperature was raised to 37 degrees C for incorporation. Aggregates incorporating dol-p or dolicol were added to a human promonocytic leukemia U937 cell suspension at 37 degrees C. When the temperature was lowered to 25 degrees 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.
Fujimoto
K
K
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan. fujimoto@applc.keio.ac.jp
Iwasaki
C
C
Arai
C
C
Kuwako
M
M
Yasugi
E
E
D000178:Acrylamides / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000737:chemistry; D053938:DNA Fragmentation / Q000187:drug effects; D016503:Drug Delivery Systems; D006801:Humans; D008027:Light; D008689:Methacrylates / Q000138:chemical synthesis* / Q000494:pharmacology; D008970:Molecular Weight; D009391:Nephelometry and Turbidimetry; D014677:Pharmaceutical Vehicles; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology; D012542:Scattering, Radiation; D013388:Succinimides / Q000138:chemical synthesis* / Q000494:pharmacology; D013696:Temperature; D020298:U937 Cells
D000178:Acrylamides; D008689:Methacrylates; D014677:Pharmaceutical Vehicles; D011108:Polymers; D013388:Succinimides; C067295:N-isopropylacrylamide; D002118:Calcium