Use of LDL receptor—targeting peptide vectors for in vitro and in vivo cargo transport across the blood‐brain barrier

Molino, Yves; David, Marion; Varini, Karine; Jabès, Françoise; Gaudin, Nicolas; Fortoul, Aude; Bakloul, Karima; Masse, Maxime; Bernard, Arnaud; Drobecq, Lucile; Lécorché, Pascaline; Temsamani, Jamal; Jacquot, Guillaume; Khrestchatisky, Michel

doi:10.1096/fj.201600827r

Cited by 82 publications

(60 citation statements)

References 55 publications

(102 reference statements)

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“…About approx. 25% or more of the total cholesterol in human body is located in the brain to maintain neuronal physiology 30) ; however, in cholesterol homeostasis in the brain, the uptake from blood circulation based on RMT has little importance in usual condition due to de novo synthesis in the brain. Notwithstanding, transendothelial drug transfer based on RMT via LDLR is useful.…”

Section: Receptor-targeting Peptides As Ligandsmentioning

confidence: 99%

Smart Strategies for Therapeutic Agent Delivery into Brain across the Blood–Brain Barrier Using Receptor-Mediated Transcytosis

Tashima¹

2020

Chem. Pharm. Bull.

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Discriminatory drug delivery into target cells is essential to effectively elicit the drug activity and to avoid off-target side effects; however, transporting drugs across the cell membrane is difficult due to factors such as molecular size, hydrophilicity, intercellular adhesiveness, and efflux transporters, particularly, in the brain capillary endothelial cells. Drug delivery into the brain is blocked by the blood-brain barrier (BBB). Thus, developing drugs for the central nervous system (CNS) diseases remains a challenge. The approach based on receptor-mediated transcytosis (RMT) can overcome this impassable problem at the BBB. Well-designed molecules for RMT form conjugates with the ligand and drugs via linkers or nanoparticles. Cell penetrating peptides (CPPs), receptor-targeting peptides, and monoclonal antibodies (mAbs) are often used as ligands. The binding of ligand to the receptor on the endothelial cell surface induces endocytosis. Existing exosomes comprising the conjugates move in the cytoplasm and fuse with the opposite plasma membrane to release them. Subsequently, the transcytosed conjugate-loaded drugs or released drugs from the conjugates elicit activity in the brain. As receptors, transferrin receptor (TfR), low-density lipoprotein receptor (LDLR), and insulin receptor (InsR) have been used to intendedly induce transcytosis. Presently, several clinical trials on CNS drugs for Alzheimer's and Parkinson disease are hindered due to poor drug distribution into the brain. Therefore, this strategy based on RMT is a promising method for CNS drugs to be transported into the brain. In this review, I introduce the practicality and possibility of drug delivery into brain across the BBB using RMT.

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Section: Receptor-targeting Peptides As Ligandsmentioning

confidence: 99%

Smart Strategies for Therapeutic Agent Delivery into Brain across the Blood–Brain Barrier Using Receptor-Mediated Transcytosis

Tashima¹

2020

Chem. Pharm. Bull.

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“…Depending on the different types of apolipoproteins present on their surface, the lipoproteins are captured by lipoprotein receptors of specific cells. Drug nanoparticles conjugated with apolipoprotein domains have been developed with limited brain penetration due to their large size and their competition with circulating endogenous ligands [108,109].…”

Section: Combinations Of Drugs Targeting Receptor-mediated Transportmentioning

confidence: 99%

How to Make Anticancer Drugs Cross the Blood–Brain Barrier to Treat Brain Metastases

Angeli

Nguyễn

Janin

et al. 2019

IJMS

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The incidence of brain metastases has increased in the last 10 years. However, the survival of patients with brain metastases remains poor and challenging in daily practice in medical oncology. One of the mechanisms suggested for the persistence of a high incidence of brain metastases is the failure to cross the blood–brain barrier of most chemotherapeutic agents, including the more recent targeted therapies. Therefore, new pharmacological approaches are needed to optimize the efficacy of anticancer drug protocols. In this article, we present recent findings in molecular data on brain metastases. We then discuss published data from pharmacological studies on the crossing of the blood–brain barrier by anticancer agents. We go on to discuss future developments to facilitate drug penetration across the blood–brain barrier for the treatment of brain metastases among cancer patients, using physical methods or physiological transporters.

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“…Additionally, the physiological activity of the receptor must be retained, and importantly, not changed as a consequence of its use as drug delivery mediator across the BBB. Among the highly expressed BBB receptors exploited for drug delivery to the brain are receptors for transferrin, 61 low-density lipoprotein, 62 and insulin. 63 A number of studies have demonstrated that the TfR and the low-density lipoprotein receptors (LDLRs) are suitable to target for drug delivery across the BBB due to the fact that these receptors may facilitate drug transcytosis.…”

Section: Receptor-mediated Transcytosismentioning

confidence: 99%

Routes for Drug Translocation Across the Blood-Brain Barrier: Exploiting Peptides as Delivery Vectors

Kristensen

Brodin

2017

Journal of Pharmaceutical Sciences

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A number of potent drugs for the treatment of brain diseases are available. However, in order for them to reach their target site of action, they must pass the blood-brain barrier (BBB). The capillary endothelium comprises the major barrier of the BBB and allows only passive permeation of some small lipophilic molecules. Brain delivery of the larger biopharmaceuticals, which today includes an increasing number of novel drug entities, is therefore restricted, both due to their molecular size and their hydrophilic nature. Thus, the development of novel drug entities intended for the treatment of brain diseases such as neurodegenerative diseases or brain cancers require a delivery strategy for overcoming the BBB before reaching its final target within the brain. Peptide-based delivery vector is an emerging tool as shuttles for drug delivery across the BBB and one may explore receptor-mediated transcytosis, adsorptive-mediated transcytosis, and the paracellular route. The latter, however, being controversial due to the risk of co-delivery of blood-borne potential harmful substances. On the other hand, a number of studies report on drug delivery across the BBB exploiting receptor-mediated transcytosis and adsorptive-mediated transcytosis, indicating that peptides and peptide vectors may be of use in a central nervous system delivery context.

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Use of LDL receptor—targeting peptide vectors for in vitro and in vivo cargo transport across the blood‐brain barrier

Cited by 82 publications

References 55 publications

Smart Strategies for Therapeutic Agent Delivery into Brain across the Blood–Brain Barrier Using Receptor-Mediated Transcytosis

Smart Strategies for Therapeutic Agent Delivery into Brain across the Blood–Brain Barrier Using Receptor-Mediated Transcytosis

How to Make Anticancer Drugs Cross the Blood–Brain Barrier to Treat Brain Metastases

Routes for Drug Translocation Across the Blood-Brain Barrier: Exploiting Peptides as Delivery Vectors

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