Cytoskeletal-antigen specific immunoliposomes: preservation of myocardial viability.
Pathological conditions such as hypoxia and inflammation can lead to the development of cell membrane-lesions. The presence of these membrane-lesions leads to egress of intracellular macromolecules as well as exposure of intracellular microenvironment to the extracellular milieu resulting in necrotic cell death. An intracellular structure that becomes exposed to the extracellular environment is myosin, a cytoskeletal antigen. We had hypothesized that cell viability can be preserved in nascent necrotic cells if the cell membrane lesions were sealed and the injurious conditions removed. Cell membrane lesion sealing and preservation of cell viability were achieved by the application of Cytoskeletal-antigen Specific ImmunoLiposomes (CSIL) as molecular "Band-Aid" that initially plugs the holes with subsequent sealing of the lesions. Anti-myosin antibody was chosen as the cytoskeleton-antigen specific antibody to develop CSILs, because antimyosin antibody is highly specific for targeting myosin exposed through myocardial cell membrane lesions in various cardiomyopathies. Liposomes are biocompatible lipid bilayer vesicles that have been used in many biological applications for several decades. This chapter will be limited to the description of CSIL therapy to ex vivo studies in adult mammalian hearts. Due to page limitations, cell culture, gene delivery and in vivo studies will not be included. Therapeutic efficacy of CSIL in preservation of myocardial viability as well as function (by left ventricular developed pressure measurements) as assessed in globally ischemic Langendorff instrumented hearts is both dose and time dependent. This approach of cell membrane lesion repair and sealing may have broader applications in other cell systems.
Patil
Vishwesh
V
Department of Pharmaceutical Sciences, Center for Cardiovascular Targeting, Bouve College of Health Sciences, Northeastern University, Boston, MA, USA.
Khudairi
Tala
T
Khaw
Ban-An
BA
D000818:Animals; D000941:Antigens / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D003599:Cytoskeleton / Q000276:immunology*; D006321:Heart / Q000187:drug effects*; D006801:Humans; D008081:Liposomes / Q000276:immunology* / Q000627:therapeutic use*; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000473:pathology; D009203:Myocardial Infarction / Q000188:drug therapy*; D009206:Myocardium / Q000166:cytology; D051381:Rats
D000941:Antigens; D008081:Liposomes