title: Plug and seal: prevention of hypoxic cardiocyte death by sealing membrane lesions with antimyosin-liposomes.
abstract: The hallmark of cell death is the development of cell membrane lesions. Such lesions in the myocardium are usually associated with acute myocardial infarction. Minimizing myocardial necrosis by thrombolytic reperfusion therapy constitutes the only major treatment to date. We envisioned a method to seal these membrane lesions using immunoliposomes as a novel adjunctive approach. An antigen to intracellular cytoskeletal myosin in hypoxic embryonic cardiocytes is used as an anchoring site, and a specific antibody on immunoliposomes as the anchor to plug and to seal the membrane lesions. H9C2 cells were used because they are cardiocytes and are propagated in tissue culture and their viability may be assessed by various methods. Viability assessed by [3H]thymidine uptake in hypoxic cardiocyte cultures (n = 6 each) treated with antimyosin-immunoliposomes (3.26 +/- 0.483 x 10(6) c.p.m.) was similar to that of normoxic cells (3.68 +/- 0.328 x 10(6) c.p.m.), but was greater than those of untreated hypoxic cells (0.115 +/- 0.155 x 10(6) c.p.m.) or hypoxic cells treated with plain liposomes (1.140 +/- 0.577 x 10(6) c.p.m.). These results were reconfirmed by trypan blue exclusion and by fluorescent, confocal and transmission electron microscopy. They indicated that cell death in hypoxic cardiocytes can be prevented by targeted cell membrane sealing. This concept of cell salvage should be applicable in the prevention of cell death in different biological systems.
authors.affiliation: Center for Drug Targeting and Analysis, Northeastern University, Boston, Massachusetts 02115, USA.
authors.forename: B A
authors.initials: BA
authors.lastname: Khaw
authors.forename: V P
authors.initials: VP
authors.lastname: Torchilin
authors.forename: I
authors.initials: I
authors.lastname: Vural
authors.forename: J
authors.initials: J
authors.lastname: Narula
mesh_terms: D000818:Animals; D000906:Antibodies; D016923:Cell Death; D015687:Cell Hypoxia; D002460:Cell Line; D002462:Cell Membrane / Q000648:ultrastructure*; D002463:Cell Membrane Permeability; D008081:Liposomes / Q000276:immunology*; D009206:Myocardium / Q000166:cytology* / Q000648:ultrastructure; D009218:Myosins / Q000276:immunology*; D051381:Rats
chemical_list: D000906:Antibodies; D008081:Liposomes; D009218:Myosins