Transferrin peptide (Tfpep) targeted gold nanoparticles (Tfpep-Au NPs) loaded with the photodynamic pro-drug, P Drug targeting through the brain capillary endothelium, which forms the blood-brain barrier (BBB) in vivo, may be achieved with peptidomimetic monoclonal antibodies that target peptide transcytosis systems on the BBB in vivo. Progress in Neurobiology 2019, 181 , 101665. Abstract. therapeutic genes/drugs to brain. CAS Article Google Scholar Such systems have been shown to be effective in animal models including primates, but no clinical trials have been performed so far. BBB drug delivery is the limiting factor in the future development of new therapeutics for the brain. Targeting Blood-brain barrier transport using a high-affinity, brain ... Rationale:The ability to treat invalidating neurological diseases is impeded by the presence of the blood-brain barrier (BBB), which inhibits the transport of most blood-borne substances into the brain parenchyma. An antibody-avidin fusion protein specific for the transferrin receptor serves as a delivery vehicle for effective brain targeting: initial applications in anti-HIV antisense drug delivery to the brain. The membrane transferrin receptor-mediated endocytosis or internalization of the complex of transferrin bound iron and the transferrin receptor is the major route of cellular iron uptake. Neurons are fragile cells with a high dependency on the homeostatic mechanisms that regulate their microenvironment. Therapeutic drug delivery across the blood-brain barrier (BBB) is not only inefficient, but also nonspecific to brain stroma. Keywords blood-brain barrier , biologics , receptor-mediated transport , antibody , transferrin receptor , insulin receptor , low density lipoprotein receptor 45 Transferrin receptor- Transferrin, a serum glycoprotein, transports iron through the blood and into cells by binding to the transferring receptor and subsequently being internalized via receptor-mediated endocytosis. We used this approach to computationally design small proteins that bind to an exposed beta sheet on the human transferrin receptor (hTfR), which shuttles interacting proteins across the blood–brain barrier (BBB), opening up avenues for drug delivery into the brain. The role of the transferrin–transferrin-receptor system in drug delivery and targeting Hongyan Li, Hongzhe Sun and Zhong Ming Qian Exploration of the potential of site-specific and target-oriented drug delivery systems has gained interest recently.Indeed,the efficient cellular mechanism of transferrin uptake has been exploited for the delivery Abstract. The membrane transferrin receptor-mediated endocytosis or internalization of the complex of transferrin bound iron … Transfer across the blood-brain barrier (BBB) remains a significant hurdle for the development of biopharmaceuticals with therapeutic effects within the central nervous system. Customized vectors for targeted drug delivery Vect-Horus’ versatile drug targeting technology uses receptor-mediated transport to deliver drugs or imaging agents to the brain and cancer tissues. The OX26 monoclonal antibody against the rat transferrin receptor offers great promise in the delivery of therapeutic agents across the blood-brain barrier to the brain and serves as a potential alternative to viral vector for gene therapy. In this study, we proposed liposomal nanoparticles modified with brain targeting ligandsfor active brain targeting with enhanced BBB permeation and delivery of genes to brain. The in-vivo results indicated that transferrin receptor-targeted theranostic liposomes could be a promising carrier for brain theranostics due to nano-sized delivery and its permeability which provided an improved and prolonged brain targeting of docetaxel and QDs in comparison to the non- targeted preparations. Transferrin receptor consists of two linked 90kDa subunits and each of them can bind transferrin molecule. An efficient strategy for brain targeted delivery is the utilization of the targeting ligand conjugated nanoparticles to trigger the receptor-mediated transcytosis. Various RMT-targeting strategies have been developed over the past 20 years, and this review explores exciting recent advances, emphasizing studies that show brain targeting in vivo. Targeting the transferrin receptor (TfR) on the surface of brain capillaries has been a popular strategy to For the past two decades, a variety of drug delivery systems has been designed to target components of the blood-brain barrier, including the transferrin receptor, a transmembrane glycoprotein highly expressed in the brain endothelium. The role of the transferrin–transferrin-receptor system in drug delivery and targeting: Trends in Pharmacological Sciences @article{osti_1816315, title = {Transferrin receptor targeting by de novo sheet extension}, author = {Sahtoe, Danny D. and Coscia, Adrian and Mustafaoglu, Nur and Miller, Lauren M. and Olal, Daniel and Vulovic, Ivan and Yu, Ta-Yi and Goreshnik, Inna and Lin, Yu-Ru and Clark, Lars and Busch, Florian and Stewart, Lance and Wysocki, Vicki H. and Ingber, … The idea is fairly simple: tether a therapy to an antibody or antibody fragment featuring a receptor, in this case for transferrin, that can carry a … Indeed, the efficient cellular mechanism of transferrin uptake has been exploited for the delivery not only of anticancer drugs and proteins, but also of therapeutic genes into proliferating malignant cells that overexpress transferrin receptors. The safest and most effective way of targeting drugs to the entire brain is via delivery systems directed at endogenous receptor-mediated uptake mechanisms present at the cerebral capillaries. The delivery of therapeutics to brain tissues is one of the main challenges in neuropathology. To explore the potential of this tumor induced expression of transferrin receptors for targeting drug carriers, in this study, I have developed and characterized liposome carriers containing paclitaxel, for targeted delivery to the glioma }, author={C. Duf{\`e}s and Majed … Direct conjugation and immunotoxin studies using the transferrin peptide or anti-transferrin receptor antibodies as the targeting moiety have established the capacity to enhance cellular uptake, cross the blood brain barrier, limit systemic toxicity and reverse multi-drug resistance. Submitted: 29 June 2015 Accepted: 10 August 2015 Published online: 10 September 2015 Keywords: α-synuclein • blood–brain barrier • drug delivery • dual targeting • immunoliposomes • peptidomimetic monoclonal antibodies • transferrin receptor An important role of the endogenous ligand, transferrin (Tf) or insulin, in receptor-mediated-transport (RMT) of the associated MAb was found and was attributed to the five order magnitude difference between plasma concentrations of Tf (25,000 nM) and insulin (0.3 nM). In spite of the rapid growth in recent years in drug development, there is still a low success rate of effective therapies focused in diseases of the central nervous system. The safest and most effective way of targeting drugs to the entire brain is via delivery systems directed at endogenous receptor-mediated uptake mechanisms present at the cerebral capillaries. Introduction While denoting the primary obstacle for delivering therapeutics to the brain 1,2, the blood-brain barrier Brain diseases are among the less understood and poorly treated conditions. through receptors present in the brain capillary endothelium. Various RMT-targeting strategies have been developed over the past 20 years, and this review explores exciting recent advances, emphasizing studies that show brain targeting in vivo. In particular, the TfR plays a significant role in brain drug and gene delivery. Targeting transferrin receptors at the blood-brain barrier improves the uptake of immunoliposomes and subsequent cargo transport into the brain parenchyma. It worked. Introduction: Biologic drugs are large molecules that do not cross the blood– brain barrier (BBB). Targeting gold nanoparticles (AuNPs) with two or more receptor binding peptides has been proposed to address intratumoral heterogeneity of glioblastomas that overexpress multiple cell surface receptors to ultimately improve therapeutic efficacy. Vect-Horus’ versatile drug targeting technology uses receptor-mediated transport to deliver drugs or … The ability to target therapeutic agents to specific tissues is an important element in the development of new disease treatments. In the present study the uptake of OX26-immunoliposomes by target cells as well as their transcytosis across the blood-brain barrier was investigated. The Tf receptor is of particular interest because its expression in capillaries throughout the body is restricted to brain capillaries ( 10 ). The receptor is a transmembrane glycoprotein with two subunits of 90 kDa that are linked by a disulfide bridge, and each of these subunits can bind to one molecule of transferrin [48] . Materials & methods: PEGylated immunoliposomes were prepared with anti-transferrin receptor OX26 and anti-alpha-synuclein LB509 antibodies to overcome the BBB in … the transferrin receptor (TfR) remains the most common target used to ensure sufficient drug delivery to the brain. Keywords To overcome this obstacle, targeting strategies binding to nutrient receptors present at the luminal membrane of the BBB are frequently employed. There are multiple receptors on the surface of BBB endothelial cells that have been targeted for the delivery of CNS-disorder medications, including the transferrin receptor (ischemic stroke, glioblastoma) and insulin receptor (Alzheimer’s disorder) [112,113,114,115,116]. Immunoliposomes conjugated with the OX26 monoclonal antibody to the rat transferrin receptor can be used for brain delivery of small molecules. The delivery of recombinant protein or gene medicines to the brain is a binary process: either the brain drug developer re-engineers the biologic with BBB drug delivery technology, or goes forward with brain drug development in the absence of a BBB delivery platform. In the present study a delivery system was developed for targeted drug delivery across the blood‑brain barrier (BBB) to the brain cancer cells. The transferrin receptor is of special interest since its expression is limited to the endothelium of the brain as opposed to peripheral endothelium. Here, we investigate the possibility of delivering immunoliposomes and their encapsulated cargo to the brain via targeting of the transferrin receptor. Keywords The transferrin receptor is responsible for the transport of iron into the brain parenchyma to maintain iron homeostasis that is of great importance for metabolism, neural conductivity, and hence, proper brain function. The transferrin receptor (TfR) is one potential target for drug delivery, as it expressed on many dividing cells and on brain endothelium, the key cellular component of the blood-brain barrier. The membrane transferrin receptor-mediated endocytosis or internalization of the complex of transferrin bound iron and … Specifically, this research work was focused on designing PEGylated liposomes surface modified with the receptor targeting protein, transferrin and cell penetrating peptides (CPPs) for targeting and improving the delivery of desired therapeutic agent to brain. Malignant glioma is the second leading cause of death from diseases of the central nervous system, threatening human health for fast development and poor prognosis.1–4 The standard clinical treatments for glioma include surgical resection, radiotherapy, chemotherapy, gene therapy, and immunotherapy.5,6 However, clinical outcome is very limited, the survival rate of p… monoclonal antibody and indicates that targeted delivery using the transferrin receptor should aim for increased mobilization of already available transferrin receptor molecules to improve tracking through the BBB. These findings suggest that transferrin receptor-targeting is a relevant strategy of increasing drug exposure to the brain. An antibody-avidin fusion protein specific for the transferrin receptor serves as a delivery vehicle for effective brain targeting: Initial applications in anti-HIV antisense drug delivery to the brain. Conclusions. Besides their efficacy during the hypoxic condition, the complexes also enhanced the selective delivery of doxorubicin up to 2.5 folds, and minimized chemoresistance, showing better tumor drug penetration than free-drug treatment.84 Transferrin (TF), a glycoprotein, is a ligand to transferrin receptor overexpressed in malignant cells. Abstract. ON THE USE OF THE TRANSFERRIN RECEPTOR AS A TARGET FOR BRAIN DRUG DELIVERY 6 Meanwhile, my work with Professor Torben Moos had progressed to include the use of liposomes for brain drug delivery, especially regarding how these (non-targeted) liposomes could accumulate in specific brain regions after experimental induction of Parkinson’s disease. Nonfenestrated These are major limitations in the effective treatment of brain cancer. The Tf receptor is of particular interest because its expression in capillaries throughout the body is restricted to brain capillaries ( 10 ). 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