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Antigenic Liposomes for Generation of Disease-specific Antibodies
Published on: October 25, 2018
Cytoskeletal-antigen specific immunoliposomes: preservation of myocardial viability
Vishwesh Patil1, Tala Khudairi, Ban-An Khaw
1Department of Pharmaceutical Sciences, Center for Cardiovascular Targeting, Bouve College of Health Sciences, Northeastern University, Boston, MA, USA.
Abstract:
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.
Insights
Cytoskeletal-antigen Specific ImmunoLiposomes (CSIL) act as a molecular "Band-Aid" to seal cell membrane lesions, preserving cell viability. This novel approach shows promise for treating conditions causing cell damage and death.
Area of Science:
- Biomedical Engineering
- Cell Biology
- Cardiovascular Research
Background:
- Pathological conditions like hypoxia and inflammation cause cell membrane lesions, leading to macromolecule leakage and necrotic cell death.
- Myosin, a cytoskeletal antigen, becomes exposed to the extracellular environment when cell membranes are compromised.
- Preserving cell viability in early necrotic cells is possible if membrane lesions are sealed and damaging conditions are removed.
Purpose of the Study:
- To investigate the therapeutic potential of Cytoskeletal-antigen Specific ImmunoLiposomes (CSIL) for sealing cell membrane lesions.
- To evaluate the efficacy of CSIL in preserving cell viability and myocardial function in ex vivo heart models.
- To explore CSIL as a novel therapeutic strategy for cell membrane repair.
Main Methods:
- Development of CSIL using anti-myosin antibodies to target exposed myosin in myocardial cell membrane lesions.
- Application of CSIL as a molecular "Band-Aid" to plug and seal cell membrane defects.
- Assessment of therapeutic efficacy in globally ischemic Langendorff instrumented adult mammalian hearts, measuring myocardial viability and function (left ventricular developed pressure).
Main Results:
- CSIL effectively sealed cell membrane lesions, preventing the egress of intracellular components.
- Preservation of myocardial viability and function was achieved using CSIL therapy.
- The therapeutic efficacy of CSIL was found to be dose and time-dependent in the ex vivo heart models.
Conclusions:
- CSIL therapy represents a promising approach for repairing and sealing cell membrane lesions.
- This method can preserve cell viability and organ function in conditions involving membrane damage.
- The cell membrane lesion repair strategy using CSIL may have broad applicability across different cell systems.
