Human complement receptor type 1–directed loading of tissue plasminogen activator on circulating erythrocytes for prophylactic fibrinolysis

Зайцев, С. В.; Danielyan, Kristina; Murciano, Juan-Carlos; Ganguly, Kumkum; Krasik, Tatiana; Taylor, Ronald P.; Pincus, Stephanie H.; Jones, Steven M.; Cines, Douglas B.; Muzykantov, Vladimir R.

doi:10.1182/blood-2005-11-012336

Cited by 61 publications

(75 citation statements)

References 62 publications

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“…Blood samples were collected and the major organs were harvested and analyzed for radioactivity as described for 125 I. Fibrinolytic Activity of Anti-GPA scFv/PA Loaded In Vivo on Circulating Carrier RBCs. We followed the protocol used previously for an anti-CR1 tPA conjugate (Zaitsev et al, 2006). In brief, equimolar doses of anti-GPA scFv/PA or PA, providing an initial blood concentration of 0.85 M (2 mg/kg PA and 4 mg/kg anti-GPA scFv/PA), were injected in 200 l of saline vehicle into anesthetized mice via the jugular vein (drug-free saline was injected as a placebo control).…”

Section: Targeting Tpa Fusion To Rbc For Prophylactic Fibrinolysismentioning

confidence: 99%

“…We measured the binding of 125 I-anti-GPA scFv/PA to mouse (target cells) versus human (negative control) RBC as described previously for an anti-CR1 monoclonal antibody/tPA conjugate (Zaitsev et al, 2006). In brief, RBCs were washed by centrifugation (1200g) with PBS/3% BSA, resuspended in the same buffer to a hematocrit of 1 or 10% and incubated with various concentrations of 125 I-scFv-PA for 1 h at 37°C (loading) with gentle rotation.…”

Section: Targeting Tpa Fusion To Rbc For Prophylactic Fibrinolysismentioning

confidence: 99%

“…Experiments were conducted under protocols approved by the Institutional Animal Care and Use Committee of the University of Pennsylvania. Washed RBCs obtained from fresh anticoagulated mouse blood were labeled with 51 Cr, as described previously (Zaitsev et al, 2006). 51 Cr-RBC or 51 Cr-RBC preloaded with 125 I-anti-GPA scFv/PA was injected into anesthetized mice via the jugular vein.…”

Section: Targeting Tpa Fusion To Rbc For Prophylactic Fibrinolysismentioning

confidence: 99%

“…This goal can be achieved by use of tPA derivatives endowed with the ability to bind safely to circulating RBCs. Thus, tPA, chemically conjugated with a monoclonal antibody specific for human complement receptor type I (CR1, an RBC glycoprotein involved in complement regulation and the clearance of immune complexes) (Fearon et al, 1989), can be safely attached onto circulating RBCs, thereby providing thromboprophylaxis in mouse models of thrombosis (Zaitsev et al, 2006). However, CR1 is a low-abundant glycoprotein with significant variation in expression levels among individuals (500 -1500 copies per human RBC) (Birmingham and Hebert, 2001).…”

mentioning

confidence: 99%

“…However, coupling tPA to carrier red blood cells (RBCs) fundamentally alters tPA pharmacokinetics, converting it from a problematic therapeutic agent into a safe and effective prophylactic agent (Murciano et al, 2003). Studies in animal models have shown that coupling of tPA to RBCs restricts access of the resultant RBC/tPA both to the CNS and to postsurgical hemostatic clots (Zaitsev et al, 2006;Danielyan et al, 2008). RBC/tPA circulate for many hours and incorporate into and rapidly dissolve newly formed, potentially occlusive clots from within (Murciano et al, 2003).…”

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confidence: 99%

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Targeting of a Mutant Plasminogen Activator to Circulating Red Blood Cells for Prophylactic Fibrinolysis

Зайцев

Spitzer

Murciano

et al. 2009

J Pharmacol Exp Ther

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Chemical coupling to carrier red blood cells (RBCs) converts tissue type plasminogen activator (tPA) from a problematic therapeutic into a safe agent for thromboprophylaxis. The goal of this study was to develop a more clinically relevant recombinant biotherapeutic by fusing a mutant tPA with a single-chain antibody fragment (scFv) with specificity for glycophorin A (GPA) on mouse RBCs. The fusion construct (anti-GPA scFv/PA) bound specifically to mouse but not human RBCs and activated plasminogen; this led to rapid and stable attachment of up to 30,000 copies of anti-GPA scFv/PA per mouse RBC that were thereby endowed with high fibrinolytic activity. Binding of anti-GPA scFv/PA neither caused RBC aggregation, hemolysis, uptake in capillary-rich lungs or in the reticuloendothelial system nor otherwise altered the circulation of RBCs. Over 40% of labeled anti-GPA scFv/PA injected in mice bound to RBC, which markedly prolonged its intravascular circulation and fibrinolytic activity compared with its nontargeted PA counterpart, anti-GPA scFv/PA, but not its nontargeted PA analog, prevented thrombotic occlusion in FeCl 3 models of vascular injury. These results provide proof-of-principle for the development of a recombinant PA variant that binds to circulating RBC and provides thromboprophylaxis by use of a clinically relevant approach.

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Section: Targeting Tpa Fusion To Rbc For Prophylactic Fibrinolysismentioning

confidence: 99%

Section: Targeting Tpa Fusion To Rbc For Prophylactic Fibrinolysismentioning

confidence: 99%

Section: Targeting Tpa Fusion To Rbc For Prophylactic Fibrinolysismentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Targeting of a Mutant Plasminogen Activator to Circulating Red Blood Cells for Prophylactic Fibrinolysis

Зайцев

Spitzer

Murciano

et al. 2009

J Pharmacol Exp Ther

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Engineering of Erythrocytes as Drug Carriers for Therapeutic Applications

Jia,

Shi,

Yan

et al. 2024

Advanced Biology

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Erythrocytes, also known as red blood cells (RBCs), have garnered considerable attention as potential carriers for drug delivery, owing to their inherent properties such as biocompatibility, biodegradability, and prolonged circulation half‐life. This paper presents a comprehensive overview of the role of erythrocytes in drug delivery, elucidating recent advancements in delivering a diverse array of therapeutic agents, including small molecules, nucleic acids, antibodies, protein enzymes, and nanoparticles. Two primary strategies for encapsulating drugs within erythrocytes are systematically discussed: internal loading and surface loading. Each strategy offers distinct advantages in terms of drug stability and release kinetics. Notably, the utilization of erythrocyte membrane camouflaged nanocarriers holds promise for enhancing the biocompatibility of conventional nanoparticles and facilitating targeted drug delivery. Furthermore, the broad spectrum of biomedical applications of erythrocyte‐based drug delivery systems are examined, ranging from cancer treatment to diabetes management, thrombosis prevention, and immunotherapy. This review provides a comprehensive evaluation of current technologies in erythrocyte‐loaded drug delivery, highlighting the strengths, weaknesses, and future directions for advancing therapeutic interventions in various disease contexts.

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Erythrocyte‐Inspired Delivery Systems

Fang

Zhang

2012

Adv Healthcare Materials

258

222

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Herein recent progress in developing red blood cell (RBC)-inspired delivery systems is reviewed, with an emphasis on how our growing understanding of fundamental biological properties of natural RBCs has been applied in the design and engineering of these delivery systems. Specifically, progress achieved in developing carrier RBCs, a class of delivery vehicles engineered by directly loading natural RBCs with therapeutic agents, will be reviewed. Then alternative approaches to engineering synthetic vehicles through mimicking the mechanobiological and chemico-biological properties of natural RBCs will be considered. The synthesis and application of RBC membrane-derived vesicles, of which the natural RBC membranes are collected and directly utilized to prepare drug carriers, will then be discussed. Finally, a recent approach in engineering RBC membrane-camouflaged nanoparticle systems that combine advantages of natural RBCs and synthetic biomaterials will be highlighted. These developments indicate that RBC-inspired delivery systems will result in next-generation nanomedicine with extensive medical applications.

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Human complement receptor type 1–directed loading of tissue plasminogen activator on circulating erythrocytes for prophylactic fibrinolysis

Cited by 61 publications

References 62 publications

Targeting of a Mutant Plasminogen Activator to Circulating Red Blood Cells for Prophylactic Fibrinolysis

Targeting of a Mutant Plasminogen Activator to Circulating Red Blood Cells for Prophylactic Fibrinolysis

Engineering of Erythrocytes as Drug Carriers for Therapeutic Applications

Erythrocyte‐Inspired Delivery Systems

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