Development of an LDL Receptor-Targeted Peptide Susceptible to Facilitate the Brain Access of Diagnostic or Therapeutic Agents

Andre, Séverine; Larbanoix, Lionel; Verteneuil, Sébastien; Stanicki, Dimitri; Nonclercq, Denis; Elst, Luce Vander; Laurent, Sophie; Müller, Robert N.; Burtéa, Carmen

doi:10.3390/biology9070161

Cited by 14 publications

(20 citation statements)

References 54 publications

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“…André et al . employed phage dodecapeptide library targeted extracellular domain of LDLR (ED-LDLR) 102 . The LDLR-targeted peptide LRPep2 (HPWCCGLRLDLR) interacted with the interface between R4 and the β-propeller (βP) domain of ED-LDLR.…”

Section: Brain Drug Delivery In Ad: Phage Display Derived-peptides Pe...mentioning

confidence: 99%

Phage display derived peptides for Alzheimer's disease therapy and diagnosis

Zhang¹,

Zhang²,

Gao³

et al. 2022

Theranostics

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Alzheimer's disease (AD) is an incurable and fatal progressive neurodegenerative disorder associated with memory and cognition impairment. AD is one of the top medical care concerns across the world with a projected economic burden of $2 trillion by 2030. To date, however, there remains no effective disease-modifying therapy available. It is more important than ever to reveal novel therapeutic approaches. Peptide-based biotherapeutics has been a great potential strategy attributed to their distinct and superior biochemical characteristics, such as reproducible chemical synthesis and modification, rapid cell and tissue permeability, and fast blood clearance. Phage display, one of today's most powerful platforms, allows selection and identification of suitable peptide drug candidates with high affinities and specificity toward target, demonstrating the potential to overcome challenges and limitations in AD diagnosis/treatment. We aim to provide the first comprehensive review to summarize the status in this research direction. The biological overview of phage display is described, including basic biology of the phage vectors and construction principle of phage library, biopanning procedure, mirror image phage display, and various binding affinity evaluation approaches. Further, the applications of phage display in AD therapy, targeted drug delivery, and early detection are presented. Finally, we discuss the current challenges and offer a future outlook for further advancing the potential application of phage display on AD and other neurodegenerative diseases.

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Section: Brain Drug Delivery In Ad: Phage Display Derived-peptides Pe...mentioning

confidence: 99%

Phage display derived peptides for Alzheimer's disease therapy and diagnosis

Zhang¹,

Zhang²,

Gao³

et al. 2022

Theranostics

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“…The structure of LRPep2 and computational docking of peptide–protein binding (top panel) and colocalization of rhodamine‐labeled LRPep2‐rho (red) with LDLR (green) on mouse brain slices (bottom panel) are shown. The LRPep2 image is reproduced with permission from André et al (2020). Copyright 2020 MDPI…”

Section: Discovery Of Bbb Shuttle Peptidesmentioning

confidence: 99%

“…A 7‐residue peptide pepC7 (CTSTSAPYC; Table 1) discovered using PDT showed brain‐homing properties and 41‐fold higher translocation efficacy than the random library phage (Li et al, 2012). Burtea et al have employed the PDT to identify a promising BBB crossing peptide sequence LRPep2 (HPWCCGLRLDLR; Table 1) that targets the extracellular domain of low‐density lipoprotein receptor (LDLR), evidenced by the immunofluorescence staining of colocalized LRPep2 with LDLR at the blood vessels on mouse brain slices (Figure 3(c); André et al, 2020). Other BBB shuttle peptides discovered by PDT, such as L57, VH4127, Peptide‐22, THR, CRT, HAI, SLS, 12‐mer‐1.2, 12‐mer‐1.3, G23, TACL08, TGN, gHoPe2, and E1‐3, are summarized in Table 1.…”

Section: Discovery Of Bbb Shuttle Peptidesmentioning

confidence: 99%

“…An 18‐residue ApoE peptide fragment and a 39‐residue ApoB peptide fragment (Table 1) were derived from the endogenous neurotropic ApoE and ApoB proteins and showed BBB penetrating effect by interacting with LDLRs in the brain (Jiang et al, 2018; Oller‐Salvia, Sánchez‐Navarro, Ciudad, et al, 2016; Zhang et al, 2010). The latest phage display biopanning also discovered several BBB shuttle peptides including Peptide‐22, VH4127, LRPep2, and AEP peptides targeting LDLR and L57 peptide targeting LRP‐1 receptor (Table 1; Al‐azzawi et al, 2019; André et al, 2020; Jacquot et al, 2016; Malcor et al, 2012; Sakamoto et al, 2017).…”

Section: Bbb Shuttle Peptides Used For Pdcsmentioning

confidence: 99%

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Brain penetrating peptides and peptide–drug conjugates to overcome the blood–brain barrier and target CNS diseases

Zhou

Smith

Liu

2021

WIREs Nanomed Nanobiotechnol

123

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Nearly one in six people worldwide suffer from disorders of the central nervous system (CNS). There is an urgent need for effective strategies to improve the success rates in CNS drug discovery and development. The lack of effective technologies for delivering drugs and genes to the brain due to the blood–brain barrier (BBB), a structural barrier that effectively blocks most neurotherapeutic agents from reaching the brain, has posed a formidable hurdle for CNS drug development. Brain‐homing and brain‐penetrating molecular transport vectors, such as brain permeable peptides or BBB shuttle peptides, have shown promise in overcoming the BBB and ferrying the drug molecules to the brain. The BBB shuttle peptides are discovered by phage display technology or derived from natural neurotropic proteins or certain viruses and harness the receptor‐mediated transcytosis molecular machinery for crossing the BBB. Brain permeable peptide–drug conjugates (PDCs), composed of BBB shuttle peptides, linkers, and drug molecules, have emerged as a promising CNS drug delivery system by taking advantage of the endogenous transcytosis mechanism and tricking the brain into allowing these bioactive molecules to pass the BBB. Here, we examine the latest development of brain‐penetrating peptide shuttles and brain‐permeable PDCs as molecular vectors to deliver small molecule drug payloads across the BBB to reach brain parenchyma. Emerging knowledge of the contribution of the peptides and their specific receptors expressed on the brain endothelial cells, choice of drug payloads, the design of PDCs, brain entry mechanisms, and delivery efficiency to the brain are highlighted. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease

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“…In recent studies, researchers have been able to simulate in vitro BBB using amniotic fluid-derived induced pluripotent stem cells (AF-iPSC) while demonstrating their superiority in transcytosis using acetylated low-density lipoprotein-like receptors (LRP1) (5). These LRP1 and high-density lipoproteins make up a complex molecule known as apolipoprotein E (ApoE), which transports cholesterol and other lipids across the BBB (41,42). To take advantage of this, grafting nanoparticles or drugs with ApoE could target LRP1 in the brain.…”

Section: Low-density Lipoprotein Receptor-related Protein 1 (Lrp1)mentioning

confidence: 99%

Multi-disciplinary Approach for Drug and Gene Delivery Systems to the Brain

et al. 2021

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Drug delivery into the brain has for long been a huge challenge as the blood–brain barrier (BBB) offers great resistance to entry of foreign substances (with drugs inclusive) into the brain. This barrier in healthy individuals is protective to the brain, disallowing noxious substances present in the blood to get to the brain while allowing for the exchange of small molecules into the brain by diffusion. However, BBB is disrupted under certain disease conditions, such as cerebrovascular diseases including acute ischemic stroke and intracerebral hemorrhage, and neurodegenerative disorders including multiple sclerosis (MS), Alzheimer’s disease (AD), Parkinson’s disease (PD), and cancers. This review aims to provide a broad overview of present-day strategies for brain drug delivery, emphasizing novel delivery systems. Hopefully, this review would inspire scientists and researchers in the field of drug delivery across BBB to uncover new techniques and strategies to optimize drug delivery to the brain. Considering the anatomy, physiology, and pathophysiological functioning of the BBB in health and disease conditions, this review is focused on the controversies drawn from conclusions of recently published studies on issues such as the penetrability of nanoparticles into the brain, and whether active targeted drug delivery into the brain could be achieved with the use of nanoparticles. We also extended the review to cover novel non-nanoparticle strategies such as using viral and peptide vectors and other non-invasive techniques to enhance brain uptake of drugs. Graphical abstract

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Development of an LDL Receptor-Targeted Peptide Susceptible to Facilitate the Brain Access of Diagnostic or Therapeutic Agents

Cited by 14 publications

References 54 publications

Phage display derived peptides for Alzheimer's disease therapy and diagnosis

Phage display derived peptides for Alzheimer's disease therapy and diagnosis

Brain penetrating peptides and peptide–drug conjugates to overcome the blood–brain barrier and target CNS diseases

Multi-disciplinary Approach for Drug and Gene Delivery Systems to the Brain

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