Niosomes decorated with dual ligands targeting brain endothelial transporters increase cargo penetration across the blood-brain barrier

Mészáros, Mária; Porkoláb, Gergő; Kiss, Lóránd; Pilbat, Ana‐Maria; Kóta, Zoltán; Kupihár, Zoltán; Kéri, Albert; Galbács, Gábor; Szabó, László; Tóth, András; Fülöp, Lívia; Csete, Mária; Sipos, Áron; Hülper, Petra; Sipos, Péter; Páli, Tibor; Rákhely, Gábor; Szabó‐Révész, Piroska; Deli, Mária A.; Veszelka, Szilvia

doi:10.1016/j.ejps.2018.07.042

Cited by 45 publications

(69 citation statements)

References 62 publications

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“…A great variety of new nanoparticles (NPs), with specific features have been under intense investigation [1][2][3][4][5][6][7][8]. Also, there are many studies on the effects of these nanoparticles within the human body [9][10][11][12], and a huge number of new nanodrugs have been approved for clinical use worldwide [13].…”

Section: Introductionmentioning

confidence: 99%

Molecular and Cellular Risk Assessment of Healthy Human Cells and Cancer Human Cells Exposed to Nanoparticles

Helal-Neto

Silva

Saldanha-Gama

et al. 2019

IJMS

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Nanodrugs have in recent years been a subject of great debate. In 2017 alone, almost 50 nanodrugs were approved for clinical use worldwide. Despite the advantages related to nanodrugs/nanomedicine, there is still a lack of information regarding the biological safety, as the real behavior of these nanodrugs in the body. In order to better understand these aspects, in this study, we evaluated the effect of polylactic acid (PLA) nanoparticles (NPs) and magnetic core mesoporous silica nanoparticles (MMSN), of 1000 nm and 50 nm, respectively, on human cells. In this direction we evaluated the cell cycle, cytochemistry, proliferation and tubulogenesis on tumor cells lines: from melanoma (MV3), breast cancer (MCF-7, MDA-MB-213), glioma (U373MG), prostate (PC3), gastric (AGS) and colon adenocarcinoma (HT-29) and non-tumor cell lines: from human melanocyte (NGM), fibroblast (FGH) and endothelial (HUVEC), respectively. The data showed that an acute exposure to both, polymeric nanoparticles or MMSN, did not show any relevant toxic effects on neither tumor cells nor non-tumor cells, suggesting that although nanodrugs may present unrevealed aspects, under acute exposition to human cells they are harmless.

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Section: Introductionmentioning

confidence: 99%

Molecular and Cellular Risk Assessment of Healthy Human Cells and Cancer Human Cells Exposed to Nanoparticles

Helal-Neto

Silva

Saldanha-Gama

et al. 2019

IJMS

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“…Niosomes are nanovesicles made of synthetic surfactants; these are more stable and less expensive than liposomes and devoid of toxicity, with an inner aqueous core where hydrophilic drugs can be loaded [11,12]. For selective brain targeting, these nanocarriers can be functionalized: on the outer surface, specific ligands can be inserted to be recognized by transporters expressed on the BBB [13,14]. N-palmitoyl-glucosamine (NPG) already proved to enhance the concentration in the brain of a drug delivered by means of colloidal systems probably by interaction with the glucose transporter GLUT-1 [15,16].…”

Section: Introductionmentioning

confidence: 99%

Niosomal Formulation of a Lipoyl-Carnosine Derivative Targeting TRPA1 Channels in Brain

et al. 2019

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The transient receptor potential akyrin type-1 (TRPA1) is a non-selective cation channel playing a pivotal role in pain sensation and neurogenic inflammation. TRPA1 channels expressed in the central nervous system (CNS) have a critical role in the modulation of cortical spreading depression (CSD), which is a key pathophysiological basis of migraine pain. ADM_09 is a recently developed lipoic acid-based TRPA1 antagonist that is able to revert oxaliplatin-induced neuropathic pain and inflammatory trigeminal allodynia. In this context, aiming at developing drugs that are able to target TRPA1 channels in the CNS and promote an antioxidant effect, permeability across the blood–brain barrier (BBB) represents a central issue. Niosomes are nanovesicles that can be functionalized with specific ligands selectively recognized by transporters expressed on the BBB. In this work, the activity of ADM_09 on neocortex cultures was studied, and an efficient formulation to cross the BBB was developed with the aim of increasing the concentration of ADM_09 into the brain and selectively delivering it to the CNS rapidly after parenteral administration.

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“…A high specificity for a treatment can then be achieved. This targeting technique has been widely used in the recent years as shown by Mészáros et al [31], Song et al [32]. Briefly, in Mészáros et al, niosomes were decorated with glutathione, alanine and glucopyranose to target blood brain barrier (BBB) transporters.…”

Section: Introductionmentioning

confidence: 99%

“…Briefly, in Mészáros et al, niosomes were decorated with glutathione, alanine and glucopyranose to target blood brain barrier (BBB) transporters. This design of the particle induced a 2-fold increase in the penetration through the BBB [31]. Song et al demonstrated the efficiency of three different ligands to increase the transcytosis through biological barriers by targeting the Neonatal Fc receptor, the transferrin receptor and the αvβ3 integrin [32].…”

Section: Introductionmentioning

confidence: 99%

Effect of small molecule signaling in PepFect14 transfection

et al. 2020

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Cell-penetrating peptides can be used to deliver oligonucleotide-based cargoes into cells. Previous studies have shown that the use of small molecule drugs could be an efficient method to increase the efficacy of delivery of oligonucleotides by cell-penetrating peptides either as targeting agents that can be used in formulation with the cell-penetrating peptide and its cargo or as cell signaling modulators that facilitates the cellular uptake of the treatment. This study presents two aims. The first aim is the identification of small molecule drugs that would induce a synergic effect on the transfection of splice correcting oligonucleotides assisted by PepFect14. The second aim is to identify the mechanisms behind the effect of small molecule drugs modulation of cell-penetrating peptide assisted transfection of oligonucleotides. Through an optimized, high-throughput luciferase assay for short oligonucleotide delivery using cell-penetrating peptides, and the simultaneous addition of a small molecule drug library, we show that three small molecule drugs (MPEP, VU0357121 and Ciproxifan) induced an increase in the transfection efficacy of PepFect14 in complex with a short single-stranded oligonucleotide in HeLa pLuc705 cells. These three drugs are described in the literature to be highly specific for their respective target receptors. However, none of those receptors are expressed in our cell line, indicating a yet non-described pathway of action for these small molecules. We show that the indicated small molecules, without interfering with the particles formed by PepFect14 and the oligonucleotide, interfere via still unidentified interactions in cell signaling, leading to an up-regulation of endocytosis and a higher efficacy in the delivery of short splice correcting oligonucleotides in complex with PepFect14.

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Niosomes decorated with dual ligands targeting brain endothelial transporters increase cargo penetration across the blood-brain barrier

Cited by 45 publications

References 62 publications

Molecular and Cellular Risk Assessment of Healthy Human Cells and Cancer Human Cells Exposed to Nanoparticles

Molecular and Cellular Risk Assessment of Healthy Human Cells and Cancer Human Cells Exposed to Nanoparticles

Niosomal Formulation of a Lipoyl-Carnosine Derivative Targeting TRPA1 Channels in Brain

Effect of small molecule signaling in PepFect14 transfection

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