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Vladimir R. Muzykantov, MD, PhD
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Founders Professor in Nanoparticle Research
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Member, Institute of Medical Engineering, University of Pennsylvania School of Medicine
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Member, Center for Cancer Pharmacology, University of Pennsylvania School of Medicine
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Member, Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine
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Member, Center for Environmental Toxicology, University of Pennsylvania School of Medicine
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Member, Cardiovascular Institute, University of Pennsylvania School of Medicine
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Vice-Chair for Faculty Development, Department of Pharmacology, University of Pennsylvania
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Founding Co-Director of the PSOM/SEAS Center for Targeted Therapeutics and Translational Nanomedicine (CT3N) , University of Pennsylvania
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Department: Systems Pharmacology and Translational Therapeutics
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Contact information
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10-105 Smilow Center for Translational Research
3e 3400 Civic Center Blvd
Philadelphia, PA 19104-5158
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3e 3400 Civic Center Blvd
Philadelphia, PA 19104-5158
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Office: 215-898-9823
32 Fax: 215-898-0868
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32 Fax: 215-898-0868
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Email:
muzykant@mail.med.upenn.edu
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muzykant@mail.med.upenn.edu
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Graduate Group Affiliations
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- Pharmacology 41
- Bioengineering e
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Publications
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Education:
21 9 M.D. 1e (Internal Medicine) c
41 First School of Medicine, Moscow, Russia, 1980.
21 a Ph.D. 19 (Biochemistry) c
4c National Cardiology Research Center, Moscow, Russia, 1985.
21 9 M.A. 1a (Honoris Causa) c
33 University of Pennsylvania, 2004.
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21 9 M.D. 1e (Internal Medicine) c
41 First School of Medicine, Moscow, Russia, 1980.
21 a Ph.D. 19 (Biochemistry) c
4c National Cardiology Research Center, Moscow, Russia, 1985.
21 9 M.A. 1a (Honoris Causa) c
33 University of Pennsylvania, 2004.
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Links
9c Search PubMed for articles
59 Lab Website
80 Primary Work Website
45 Pharmacological Sciences Graduate Group Faculty
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Permanent link9c Search PubMed for articles
59 Lab Website
80 Primary Work Website
45 Pharmacological Sciences Graduate Group Faculty
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30 Drug/gene targeting and vascular biology
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366 Particular areas of interest/expertise include the recognition of surface antigens on normal or pathologically altered endothelial cells; vascular inflammation and leukocytes adhesion; mechanisms of oxidative stress and antioxidant protection of the endothelium; evaluation of specific markers of endothelial injury; immunotargeting of antioxidant enzymes, fibrinolytics and genes to the pulmonary endothelium; pulmonary pathophysiology; lung ischemia/reperfusion; prolongation of enzymes life-time in the bloodstream; controlled elimination of radiolabeled antibodies or pathogens from the bloodstream; exploration of red blood cells as carriers for prolonged circulation and site-specific delivery of drugs (fibrinolytics and anticoagulants); regulation of fibrinolysis and complement; mechanisms and regulation of intracellular targeting/trafficking of drugs.
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18 Research Summary
65f The laboratory is focused on several projects. First is the targeting of drugs (enzymes either degrading or generating oxidants, fibrinolytics, interferon, antisense oligos and genes) to the pulmonary vascular endothelium. The purpose is to develop strategies for controlled site-specific delivery of a drug to the defined subcellular compartments of the pulmonary endothelium. For example, genetic material must be delivered into the nucleus, antioxidants must accumulate in the cytoplasm, and fibrinolytics must avoid internalization. We therefore study how carrier antibodies and their derivatives recognize endothelium, and characterize cellular trafficking and local effects of the targeted agents in cell cultures, perfused animal lungs and in intact animals. Our research includes identification of the molecules localized on the surface of endothelium useful as targets for drug delivery to either normal or pathologically challenged endothelium. Endothelium-specific antigens may serve as such targets. Affinity carriers that are currently explored in our laboratory include monoclonal antibodies (and their fragments) to: angiotensin-converting enzyme (ACE), thrombomodulin and surface adhesion molecules, ICAM, PECAM, P- and E-selectins. We have characterized carriers and their modifications providing: i) a drug with an affinity to endothelium (recognition and targeting) and, ii) drug delivery in a proper cellular compartment (sub-cellular addressing). Targeting to either surface (by non-internalizable carriers) or intracellularly has been documented in cell culture, perfused lungs and in rodents in vivo.
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3bf Secondly, we explore red blood cells (RBC) as natural carriers for drugs. We have developed an original methodology for effective conjugation of large amounts of a drug (e.g., fibrinoytic enzymes or receptors for plasminogen activators) on RBC, without loss of biocompatibility of the complex. Conjugation provides prolongation of half-life of plasminogen activators in vivo by orders of magnitude and offers specific transfer of the conjugated protein (tPA, uPA-receptor) to the pulmonary endothelium. Both mechanism of the transfer (tentatively via exchange of GPI-anchored membrane proteins between RBC and endothelium) and potential therapeutic applications of RBC-conjugated fibrinolytics (treatment/prevention of pulmonary embolism/deep vein thrombosis) are in the focus of the research. We also explore RBC as carriers for intracellular drug delivery in phagocyte cells in the reticuloendothelial tissue (liver and spleen) and endothelial cells.
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Description of Research Expertise
25 Research Interests:30 Drug/gene targeting and vascular biology
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366 Particular areas of interest/expertise include the recognition of surface antigens on normal or pathologically altered endothelial cells; vascular inflammation and leukocytes adhesion; mechanisms of oxidative stress and antioxidant protection of the endothelium; evaluation of specific markers of endothelial injury; immunotargeting of antioxidant enzymes, fibrinolytics and genes to the pulmonary endothelium; pulmonary pathophysiology; lung ischemia/reperfusion; prolongation of enzymes life-time in the bloodstream; controlled elimination of radiolabeled antibodies or pathogens from the bloodstream; exploration of red blood cells as carriers for prolonged circulation and site-specific delivery of drugs (fibrinolytics and anticoagulants); regulation of fibrinolysis and complement; mechanisms and regulation of intracellular targeting/trafficking of drugs.
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18 Research Summary
65f The laboratory is focused on several projects. First is the targeting of drugs (enzymes either degrading or generating oxidants, fibrinolytics, interferon, antisense oligos and genes) to the pulmonary vascular endothelium. The purpose is to develop strategies for controlled site-specific delivery of a drug to the defined subcellular compartments of the pulmonary endothelium. For example, genetic material must be delivered into the nucleus, antioxidants must accumulate in the cytoplasm, and fibrinolytics must avoid internalization. We therefore study how carrier antibodies and their derivatives recognize endothelium, and characterize cellular trafficking and local effects of the targeted agents in cell cultures, perfused animal lungs and in intact animals. Our research includes identification of the molecules localized on the surface of endothelium useful as targets for drug delivery to either normal or pathologically challenged endothelium. Endothelium-specific antigens may serve as such targets. Affinity carriers that are currently explored in our laboratory include monoclonal antibodies (and their fragments) to: angiotensin-converting enzyme (ACE), thrombomodulin and surface adhesion molecules, ICAM, PECAM, P- and E-selectins. We have characterized carriers and their modifications providing: i) a drug with an affinity to endothelium (recognition and targeting) and, ii) drug delivery in a proper cellular compartment (sub-cellular addressing). Targeting to either surface (by non-internalizable carriers) or intracellularly has been documented in cell culture, perfused lungs and in rodents in vivo.
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3bf Secondly, we explore red blood cells (RBC) as natural carriers for drugs. We have developed an original methodology for effective conjugation of large amounts of a drug (e.g., fibrinoytic enzymes or receptors for plasminogen activators) on RBC, without loss of biocompatibility of the complex. Conjugation provides prolongation of half-life of plasminogen activators in vivo by orders of magnitude and offers specific transfer of the conjugated protein (tPA, uPA-receptor) to the pulmonary endothelium. Both mechanism of the transfer (tentatively via exchange of GPI-anchored membrane proteins between RBC and endothelium) and potential therapeutic applications of RBC-conjugated fibrinolytics (treatment/prevention of pulmonary embolism/deep vein thrombosis) are in the focus of the research. We also explore RBC as carriers for intracellular drug delivery in phagocyte cells in the reticuloendothelial tissue (liver and spleen) and endothelial cells.
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1af Zaleski MH, Omo-Lamai S, Nong J, Chase LS, Myerson JW, Glassman PM, Lee F, Reyes-Esteves S, Wang Z, Patel MN, Peshkova AD, Komatsu H, Axelsen PH, Muzykantov VR, Marcos-Contreras OA, Brenner JS.: Nanocarriers' repartitioning of drugs between blood subcompartments as a mechanism of improving pharmacokinetics, safety, and efficacy. J Control Release Oct 2024.
197 Hamideh Parhiz 1 5, Vladimir V. Shuvaev 2, Qin Li 1, Tyler E. Papp 1, Awurama A. Akyianu 1, Ruiqi Shi 1, Amir Yadegari 1, Hamna Shahnawaz 1, Sean C. Semple 3, Barbara L. Mui 3, Drew Weissman 1, Vladimir R. Muzykantov 2, Patrick M. Glassman : Physiologically based modeling of LNP-mediated delivery of mRNA in the vascular system. Mol Ther Nucleic Acids 3e Science Direct, 35(2): 102175, June 2024.
177 Hyun-Su Lee a, Ye Chan Kim a, Zhicheng Wang d, Jacob S. Brenner d, Vladimir R. Muzykantov e, Jacob W. Myerson e, Russell J. Composto: Controlling spatial distribution of functional lipids in a supported lipid bilayer prepared from vesicles. J Colloid Interface Sci. ELSEVIER, 664: 1042-1055, June 2024.
239 John C Greenwood 1 2, Fatima M Talebi 1, David H Jang 1, Audrey E Spelde 2, Emily K Gordon 2, Jiri Horak 2, Michael A Acker 3, Todd J Kilbaugh 4, Frances S Shofer 5, John G T Augoustides 2, Jacob S Brenner 6, Vladimir R Muzykantov 7, Jan Bakker 8, Benjamin S Abella: Anaerobic Lactate Production Is Associated With Decreased Microcirculatory Blood Flow and Decreased Mitochondrial Respiration Following Cardiovascular Surgery With Cardiopulmonary Bypass. Crit Care Med. 52: 1239-1250, April 2024.
179 Brian M. Leonard 1,Vladimir V. Shuvaev 2,Trent A. Bullock 1,Kalpani N. Udeni Galpayage Dona 3,Vladimir R. Muzykantov 2,Allison M. Andrews 1,3,4 andServio H. Ramirez : Engineered Dual Antioxidant Enzyme Complexes Targeting ICAM-1 on Brain Endothelium Reduce Brain Injury-Associated Neuroinflammation. Bioengineering (Basel) 48 MDPI Bioengineering (eds.). 11: 200, February 2024.
214 John C Greenwood 1, Fatima M Talebi 2, David H Jang 2, Audrey E Spelde 3, Emily K Gordon 3, Jiri Horak 3, Michael A Acker 4, Todd J Kilbaugh 5, Frances S Shofer 6, John G T Augoustides 3, Jan Bakker 7, Jacob S Brenner 8, Vladimir R Muzykantov 9, Benjamin S Abella 2: Low postoperative perfused vessel density is associated with increased soluble endothelial cell adhesion molecules during circulatory shock after cardiac surgery. Microvasc Res. 150, Nov 2023.
145 Oscar A. Marcos-Contreras, Jacob W. Myerson, Jia Nong, Jacob Samuel Brenner, Vladimir R. Muzykantov, and Patrick M. Glassman: Effective Prevention of Arterial Thrombosis with Albumin-Thrombin Inhibitor Conjugates. Mol Pharm 20(11): 5243-5946, Oct 2023.
1f8 Riera-Domingo C, Leite-Gomes E, Charatsidou I, Zhao P, Carrá G, Cappellesso F, Mourao L, De Schepper M, Liu D, Serneels J, Alameh MG, Shuvaev VV, Geukens T, Isnaldi E, Prenen H, Weissman D, Muzykantov VR, Soenen S, Desmedt C, Scheele CLGJ, Sablina A, Di Matteo M, Martín-Pérez R, Mazzone M.: Breast tumors interfere with endothelial TRAIL at the premetastatic niche to promote cancer cell seeding. Sci Adv 9: eadd5028, Mar 2023.
191 Reyes-Esteves S, Nong J, Glassman PM, Omo-Lamai S, Ohashi S, Myerson JW, Zamora ME, Ma X, Kasner SE, Sansing L, Muzykantov VR, Marcos-Contreras OA, Brenner JS.: Targeted drug delivery to the brain endothelium dominates over passive delivery via vascular leak in experimental intracerebral hemorrhage. J Control Release Mar 2023.
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Selected Publications
15b Zaleski MH, Chase LS, Hood ED, Wang Z, Nong J, Espy CL, Zamora ME, Wu J, Morrell LJ, Muzykantov VR, Myerson JW, Brenner JS.: Conjugation Chemistry Markedly Impacts Toxicity and Biodistribution of Targeted Nanoparticles, Mediated by Complement Activation. Adv Mater Feb 2025.1af Zaleski MH, Omo-Lamai S, Nong J, Chase LS, Myerson JW, Glassman PM, Lee F, Reyes-Esteves S, Wang Z, Patel MN, Peshkova AD, Komatsu H, Axelsen PH, Muzykantov VR, Marcos-Contreras OA, Brenner JS.: Nanocarriers' repartitioning of drugs between blood subcompartments as a mechanism of improving pharmacokinetics, safety, and efficacy. J Control Release Oct 2024.
197 Hamideh Parhiz 1 5, Vladimir V. Shuvaev 2, Qin Li 1, Tyler E. Papp 1, Awurama A. Akyianu 1, Ruiqi Shi 1, Amir Yadegari 1, Hamna Shahnawaz 1, Sean C. Semple 3, Barbara L. Mui 3, Drew Weissman 1, Vladimir R. Muzykantov 2, Patrick M. Glassman : Physiologically based modeling of LNP-mediated delivery of mRNA in the vascular system. Mol Ther Nucleic Acids 3e Science Direct, 35(2): 102175, June 2024.
177 Hyun-Su Lee a, Ye Chan Kim a, Zhicheng Wang d, Jacob S. Brenner d, Vladimir R. Muzykantov e, Jacob W. Myerson e, Russell J. Composto: Controlling spatial distribution of functional lipids in a supported lipid bilayer prepared from vesicles. J Colloid Interface Sci. ELSEVIER, 664: 1042-1055, June 2024.
239 John C Greenwood 1 2, Fatima M Talebi 1, David H Jang 1, Audrey E Spelde 2, Emily K Gordon 2, Jiri Horak 2, Michael A Acker 3, Todd J Kilbaugh 4, Frances S Shofer 5, John G T Augoustides 2, Jacob S Brenner 6, Vladimir R Muzykantov 7, Jan Bakker 8, Benjamin S Abella: Anaerobic Lactate Production Is Associated With Decreased Microcirculatory Blood Flow and Decreased Mitochondrial Respiration Following Cardiovascular Surgery With Cardiopulmonary Bypass. Crit Care Med. 52: 1239-1250, April 2024.
179 Brian M. Leonard 1,Vladimir V. Shuvaev 2,Trent A. Bullock 1,Kalpani N. Udeni Galpayage Dona 3,Vladimir R. Muzykantov 2,Allison M. Andrews 1,3,4 andServio H. Ramirez : Engineered Dual Antioxidant Enzyme Complexes Targeting ICAM-1 on Brain Endothelium Reduce Brain Injury-Associated Neuroinflammation. Bioengineering (Basel) 48 MDPI Bioengineering (eds.). 11: 200, February 2024.
214 John C Greenwood 1, Fatima M Talebi 2, David H Jang 2, Audrey E Spelde 3, Emily K Gordon 3, Jiri Horak 3, Michael A Acker 4, Todd J Kilbaugh 5, Frances S Shofer 6, John G T Augoustides 3, Jan Bakker 7, Jacob S Brenner 8, Vladimir R Muzykantov 9, Benjamin S Abella 2: Low postoperative perfused vessel density is associated with increased soluble endothelial cell adhesion molecules during circulatory shock after cardiac surgery. Microvasc Res. 150, Nov 2023.
145 Oscar A. Marcos-Contreras, Jacob W. Myerson, Jia Nong, Jacob Samuel Brenner, Vladimir R. Muzykantov, and Patrick M. Glassman: Effective Prevention of Arterial Thrombosis with Albumin-Thrombin Inhibitor Conjugates. Mol Pharm 20(11): 5243-5946, Oct 2023.
1f8 Riera-Domingo C, Leite-Gomes E, Charatsidou I, Zhao P, Carrá G, Cappellesso F, Mourao L, De Schepper M, Liu D, Serneels J, Alameh MG, Shuvaev VV, Geukens T, Isnaldi E, Prenen H, Weissman D, Muzykantov VR, Soenen S, Desmedt C, Scheele CLGJ, Sablina A, Di Matteo M, Martín-Pérez R, Mazzone M.: Breast tumors interfere with endothelial TRAIL at the premetastatic niche to promote cancer cell seeding. Sci Adv 9: eadd5028, Mar 2023.
191 Reyes-Esteves S, Nong J, Glassman PM, Omo-Lamai S, Ohashi S, Myerson JW, Zamora ME, Ma X, Kasner SE, Sansing L, Muzykantov VR, Marcos-Contreras OA, Brenner JS.: Targeted drug delivery to the brain endothelium dominates over passive delivery via vascular leak in experimental intracerebral hemorrhage. J Control Release Mar 2023.
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