Selective rat lung endothelial targeting with a new set of monoclonal antibodies to angiotensin I-converting enzyme

Balyasnikova, Irina V.; Metzger, Roman; Visintine, David J.; Dimasius, Vidas; Sun, Zhu Li; Berestetskaya, Yuliya V.; McDonald, Timothy D.; Curiel, David T.; Minshall, Richard D.; Danilov, Sergei M.

doi:10.1016/j.pupt.2004.12.008

Cited by 28 publications

(21 citation statements)

References 37 publications

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“…As an example of this concept, similar carriers directed to a membrane-proximal epitope of a related molecule (PECAM-1) lacked binding to cultured ECs vs. carriers targeted to membrane-distal epitopes, despite similar binding when presented as free counterparts (Garnacho et al 2008b). In another study the efficiency of ACE binding to endothelum in vivo varied greatly depending on the epitope targeted (Balyasnikova et al 2005). …”

Section: Discussionmentioning

confidence: 99%

Comparative binding, endocytosis, and biodistribution of antibodies and antibody‐coated carriers for targeted delivery of lysosomal enzymes to ICAM‐1 versus transferrin receptor

Papademetriou

Garnacho

Serrano

et al. 2012

J of Inher Metab Disea

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Targeting lysosomal enzymes to receptors involved in transport into and across cells holds promise to enhance peripheral and brain delivery of enzyme replacement therapies for lysosomal storage disorders. Receptors being explored include those associated with clathrin-mediated pathways, yet other pathways seem also viable. Well characterized examples are that of transferrin receptor (TfR) and intercellular adhesion molecule 1 (ICAM-1), involved in iron transport and leukocyte extravasation, respectively. TfR and ICAM-1 support ERT delivery via clathrin- vs. cell adhesion molecule-mediated mechanisms, displaying different valency and size restrictions. To comparatively assess this, we used antibodies vs. larger multivalent antibody-coated carriers and evaluated TfR vs. ICAM-1 binding and endocytosis in endothelial cells, as well as in vivo biodistribution and delivery of a model lysosomal enzyme required in peripheral organs and brain: acid sphingomyelinase (ASM), deficient in types A–B Niemann Pick disease. We found similar binding of antibodies to both receptors under control conditions, with enhanced binding to activated endothelium for ICAM-1, yet only anti-TfR induced endocytosis efficiently. Contrarily, antibody-coated carriers showed enhanced binding, engulfment, and endocytosis for ICAM-1. In mice, anti-TfR enhanced brain targeting over anti-ICAM, with an opposite outcome in the lungs, while carriers enhanced ICAM-1 targeting over TfR in both organs. Both targeted carriers enhanced ASM delivery to the brain and lungs vs. free ASM, with greater enhancement for anti-ICAM carriers. Therefore, targeting TfR or ICAM-1 improves lysosomal enzyme delivery. Yet, TfR targeting may be more efficient for smaller conjugates or fusion proteins, while ICAM-1 targeting seems superior for multivalent carrier formulations.

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Section: Discussionmentioning

confidence: 99%

Comparative binding, endocytosis, and biodistribution of antibodies and antibody‐coated carriers for targeted delivery of lysosomal enzymes to ICAM‐1 versus transferrin receptor

Papademetriou

Garnacho

Serrano

et al. 2012

J of Inher Metab Disea

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“…80 Angiotensin I-converting enzyme is expressed in 100% of alveolar capillary ECs compared with 10% of systemic capillary ECs (including those of the bronchial circulation). 81 Activated leukocyte cell adhesion molecule (ALCAM, also known as CD166) is expressed in rat lung capillary endothelium, but not in larger pulmonary vessels. 80 Alveolar capillary ECs express PECAM-1/CD31 and CD34, but not vWF.…”

Section: Pulmonary Vesselsmentioning

confidence: 99%

Phenotypic Heterogeneity of the Endothelium

Aird¹

2007

Circulation Research

981

736

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Abstract-Endothelial cells, which form the inner cellular lining of blood vessels and lymphatics, display remarkable heterogeneity in structure and function. This is the second of a 2-part review on the phenotypic heterogeneity of blood vessel endothelial cells. The first part discusses the scope, the underlying mechanisms, and the diagnostic and therapeutic implications of phenotypic heterogeneity. Here, these principles are applied to an understanding of organ-specific phenotypes in representative vascular beds including arteries and veins, heart, lung, liver, and kidney. The goal is to underscore the importance of site-specific properties of the endothelium in mediating homeostasis and focal vascular pathology, while at the same time emphasizing the value of approaching the endothelium as an integrated system. (Circ Res. 2007;100: 174-190.)

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“…Oxidants, cytokines, and other pathological agents suppress ACE expression and thus inhibit targeting to ACE (Watanabe et al 1992; Atochina et al 1992). Monoclonal anti-ACE with species specificity including rat, mouse, cat, primate, and human ACE selectively accumulate in the pulmonary vasculature after IV injection in these species (Danilov et al 2001, 1989; Balyasnikova et al 2005, 2006). Pilot safety tests have not revealed overt harmful effects of injection of anti-ACE in normal animals and humans (Danilov et al 1994; Muzykantov and Danilov 1995).…”

Section: Surface Determinants For Endothelial Targetingmentioning

confidence: 99%

Targeted delivery of therapeutics to endothelium

2008

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The endothelium is a target for therapeutic and diagnostic interventions in a plethora of human disease conditions including ischemia, inflammation, edema, oxidative stress, thrombosis and hemorrhage, and metabolic and oncological diseases. Unfortunately, drugs have no affinity to the endothelium, thereby limiting the localization, timing, specificity, safety, and effectiveness of therapeutic interventions. Molecular determinants on the surface of resting and pathologically altered endothelial cells, including cell adhesion molecules, peptidases, and receptors involved in endocytosis, can be used for drug delivery to the endothelial surface and into intracellular compartments. Drug delivery platforms such as protein conjugates, recombinant fusion constructs, targeted liposomes, and stealth polymer carriers have been designed to target drugs and imaging agents to these determinants. We review endothelial target determinants and drug delivery systems, describe parameters that control the binding of drug carriers to the endothelium, and provide examples of the endothelial targeting of therapeutic enzymes designed for the treatment of acute vascular disorders including ischemia, oxidative stress, inflammation, and thrombosis.

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Selective rat lung endothelial targeting with a new set of monoclonal antibodies to angiotensin I-converting enzyme

Cited by 28 publications

References 37 publications

Comparative binding, endocytosis, and biodistribution of antibodies and antibody‐coated carriers for targeted delivery of lysosomal enzymes to ICAM‐1 versus transferrin receptor

Comparative binding, endocytosis, and biodistribution of antibodies and antibody‐coated carriers for targeted delivery of lysosomal enzymes to ICAM‐1 versus transferrin receptor

Phenotypic Heterogeneity of the Endothelium

Targeted delivery of therapeutics to endothelium

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