Novel Peptides Derived from Dengue Virus Capsid Protein Translocate Reversibly the Blood–Brain Barrier through a Receptor-Free Mechanism

Neves, Vera; Aires-da-Silva, Frederico; Morais, Maurício; Gano, Lurdes; Ribeiro, Elisabete; Pinto, A. M. P.; Aguiar, Sandra I.; Gaspar, Diana; Fernandes, Célia; Correia, João D. G.; Castanho, Miguel A. R. B.

doi:10.1021/acschembio.7b00087

Cited by 36 publications

(71 citation statements)

References 57 publications

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“…The most recent peptide shuttle reported is PepH3, a cationic peptide derived from Dengue virus type-2 capsid protein (DEN2C) [121]. In Neves et al study, the in vitro BBB transmigration after 24 h was 67.2%.…”

Section: The Role Of Bbb Peptide-shuttlesmentioning

confidence: 99%

Antibodies for the Treatment of Brain Metastases, a Dream or a Reality?

et al. 2020

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The incidence of brain metastases (BM) in cancer patients is increasing. After diagnosis, overall survival (OS) is poor, elicited by the lack of an effective treatment. Monoclonal antibody (mAb)-based therapy has achieved remarkable success in treating both hematologic and non-central-nervous system (CNS) tumors due to their inherent targeting specificity. However, the use of mAbs in the treatment of CNS tumors is restricted by the blood–brain barrier (BBB) that hinders the delivery of either small-molecules drugs (sMDs) or therapeutic proteins (TPs). To overcome this limitation, active research is focused on the development of strategies to deliver TPs and increase their concentration in the brain. Yet, their molecular weight and hydrophilic nature turn this task into a challenge. The use of BBB peptide shuttles is an elegant strategy. They explore either receptor-mediated transcytosis (RMT) or adsorptive-mediated transcytosis (AMT) to cross the BBB. The latter is preferable since it avoids enzymatic degradation, receptor saturation, and competition with natural receptor substrates, which reduces adverse events. Therefore, the combination of mAbs properties (e.g., selectivity and long half-life) with BBB peptide shuttles (e.g., BBB translocation and delivery into the brain) turns the therapeutic conjugate in a valid approach to safely overcome the BBB and efficiently eliminate metastatic brain cells.

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Section: The Role Of Bbb Peptide-shuttlesmentioning

confidence: 99%

Antibodies for the Treatment of Brain Metastases, a Dream or a Reality?

et al. 2020

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“…It is worth stressing that cell penetration differs from cell translocation, meaning that a CPP can be competent in intracellular delivery but fail in epithelial translocation [ 29 ]. For instance, the ten most widely studied membrane-active peptides have a tendency to accumulate unspecifically into different cell lines and, consequently, in different organs, leading to undesired effects [ 30 ].…”

Section: Introductionmentioning

confidence: 99%

“…An additional study was performed using the four α-helical domains of the DEN2C protein (α1, α2, α3 and α4) to identify trans-BBB peptides. PepH3 α3 sequence (AGILKRW) achieved high brain uptake [ 29 ]. PepH3, a hydrophobic peptide, is able to transcytose across the cell, while other peptides accumulate inside the endothelial membrane.…”

Section: Introductionmentioning

confidence: 99%

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A New Noncanonical Anionic Peptide That Translocates a Cellular Blood–Brain Barrier Model

et al. 2017

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The capacity to transport therapeutic molecules across the blood–brain barrier (BBB) represents a breakthrough in the development of tools for the treatment of many central nervous system (CNS)-associated diseases. The BBB, while being protective against infectious agents, hinders the brain uptake of many drugs. Hence, finding safe shuttles able to overcome the BBB is of utmost importance. Herein, we identify a new BBB-translocating peptide with unique properties. For years it was thought that cationic sequences were mandatory for a cell-penetrating peptide (CPP) to achieve cellular internalization. Despite being anionic at physiological pH, PepNeg (sequence (SGTQEEY) is an efficient BBB translocator that is able to carry a large cargo (27 kDa), while maintaining BBB integrity. In addition, PepNeg is able to use two distinct methods of translocation, energy-dependent and -independent, suggesting that direct penetration might occur when low concentrations of peptide are presented to cells. The discovery of this new anionic trans-BBB peptide allows the development of new delivery systems to the CNS and contributes to the need to rethink the role of electrostatic attraction in BBB-translocation.

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“…administration in CD1 mice and bio-distribution was measured in mice sacrificed 5 min and 1 h after administration. Furthermore, its clearance and excretion is relatively fast, making it a good candidate for a shuttle carrier [33]. Spontaneous internalisation of nanowires (NW), linked with a cell penetrating peptide: the trans-activating transcriptional activator (TAT) from human immunodeficiency virus 1, has also been reported [34].…”

Section: Novel Shuttle Peptidesmentioning

confidence: 99%

Peptide based drug delivery systems to the brain

Islam

Leach

Smith³

et al. 2020

Nano Express

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With estimated worldwide cost over $1 trillion just for dementia, diseases of the central nervous system pose a major problem to health and healthcare systems, with significant socio-economic implications for sufferers and society at large. In the last two decades, numerous strategies and technologies have been developed and adapted to achieve drug penetration into the brain, evolving alongside our understanding of the physiological barriers between the brain and surrounding tissues. The blood brain barrier (BBB) has been known as the major barrier for drug delivery to the brain. Both invasive and minimally-invasive approaches have been investigated extensively, with the minimallyinvasive approaches to drug delivery being more suitable. Peptide based brain targeting has been explored extensively in the last two decades. In this review paper, we focused on self-assembled peptides, shuttle peptides and nanoparticles drug delivery systems decorated/conjugated with peptides for brain penetration.Abbreviations

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Novel Peptides Derived from Dengue Virus Capsid Protein Translocate Reversibly the Blood–Brain Barrier through a Receptor-Free Mechanism

Cited by 36 publications

References 57 publications

Antibodies for the Treatment of Brain Metastases, a Dream or a Reality?

Antibodies for the Treatment of Brain Metastases, a Dream or a Reality?

A New Noncanonical Anionic Peptide That Translocates a Cellular Blood–Brain Barrier Model

Peptide based drug delivery systems to the brain

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