Use of cytoskeleton-specific immunoliposomes for preservation of cell viability and gene delivery

Pathological conditions such as hypoxia and inflammation provoke cell membr ane lesions representing sub-microscopic holes through which components of cytoskeleton become exposed to the extracellular mileur. Cytoskeleton-speci fic antibodies coupled to liposomes can deliver the phospholipid vesicles t o such lesions. We have used the in vitro delivery of antimyosin antibody-m ediated liposomes to hypoxic cardiomyocytes in order: (1) to prevent cell d eath by sealing membrane lesions, and (2) to provide a novel method of intr acellular delivery of DNA. A hypoxic model of injury in H9C2 rat embryonic cardiocytes was used in our experiments. Treatment with antimyosin-immunoli posomes improved the survival of these hypoxic cells significantly relative to controls. Under this artificially induced stress, cytoskeleton-specific immunoliposomes can also deliver their intraliposomal contents into the cy toplasm of the target cells, providing an excellent opportunity for the dev elopment of a method for the targeted intracellular delivery of drugs and g eneric constructs. This potential was confirmed by demonstration of efficie nt intracellular delivery of antimyosin sFc vector pGL2 luciferase vector a nd bacterial beta galactosidase vector into hypoxic cells with concomitant restoration of cell viability.