Targeting Human Endothelial Cells with Glutathione and Alanine Increases the Crossing of a Polypeptide Nanocarrier through a Blood–Brain Barrier Model and Entry to Human Brain Organoids
Nanoparticles (NPs) are the focus of research efforts that aim to develop successful drug delivery systems for the brain. Polypeptide nanocarriers are versatile platforms and combine high functionality with good biocompatibility and biodegradability. The key to the efficient brain delivery of NPs is...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/3/503 |
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| author | Mária Mészáros Thi Ha My Phan Judit P. Vigh Gergő Porkoláb Anna Kocsis Emese K. Páli Tamás F. Polgár Fruzsina R. Walter Silvia Bolognin Jens C. Schwamborn Jeng-Shiung Jan Mária A. Deli Szilvia Veszelka |
| author_facet | Mária Mészáros Thi Ha My Phan Judit P. Vigh Gergő Porkoláb Anna Kocsis Emese K. Páli Tamás F. Polgár Fruzsina R. Walter Silvia Bolognin Jens C. Schwamborn Jeng-Shiung Jan Mária A. Deli Szilvia Veszelka |
| author_sort | Mária Mészáros |
| collection | DOAJ |
| description | Nanoparticles (NPs) are the focus of research efforts that aim to develop successful drug delivery systems for the brain. Polypeptide nanocarriers are versatile platforms and combine high functionality with good biocompatibility and biodegradability. The key to the efficient brain delivery of NPs is the specific targeting of cerebral endothelial cells that form the blood–brain barrier (BBB). We have previously discovered that the combination of two different ligands of BBB nutrient transporters, alanine and glutathione, increases the permeability of vesicular NPs across the BBB. Our aim here was to investigate whether the combination of these molecules can also promote the efficient transfer of 3-armed poly(<span style="font-variant: small-caps;">l</span>-glutamic acid) NPs across a human endothelial cell and brain pericyte BBB co-culture model. Alanine and glutathione dual-targeted polypeptide NPs showed good cytocompatibility and elevated cellular uptake in a time-dependent and active manner. Targeted NPs had a higher permeability across the BBB model and could subsequently enter midbrain-like organoids derived from healthy and Parkinson’s disease patient-specific stem cells. These results indicate that poly(<span style="font-variant: small-caps;">l</span>-glutamic acid) NPs can be used as nanocarriers for nervous system application and that the right combination of molecules that target cerebral endothelial cells, in this case alanine and glutathione, can facilitate drug delivery to the brain. |
| first_indexed | 2024-03-11T09:49:20Z |
| format | Article |
| id | doaj.art-942225ea0750420d97ee9811d5594db0 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T09:49:20Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-942225ea0750420d97ee9811d5594db02023-11-16T16:22:34ZengMDPI AGCells2073-44092023-02-0112350310.3390/cells12030503Targeting Human Endothelial Cells with Glutathione and Alanine Increases the Crossing of a Polypeptide Nanocarrier through a Blood–Brain Barrier Model and Entry to Human Brain OrganoidsMária Mészáros0Thi Ha My Phan1Judit P. Vigh2Gergő Porkoláb3Anna Kocsis4Emese K. Páli5Tamás F. Polgár6Fruzsina R. Walter7Silvia Bolognin8Jens C. Schwamborn9Jeng-Shiung Jan10Mária A. Deli11Szilvia Veszelka12Institute of Biophysics, Biological Research Centre, Eötvös Loránd Research Network, H-6726 Szeged, HungaryDepartment of Chemical Engineering, National Cheng Kung University, Tainan 70101, TaiwanInstitute of Biophysics, Biological Research Centre, Eötvös Loránd Research Network, H-6726 Szeged, HungaryInstitute of Biophysics, Biological Research Centre, Eötvös Loránd Research Network, H-6726 Szeged, HungaryInstitute of Biophysics, Biological Research Centre, Eötvös Loránd Research Network, H-6726 Szeged, HungaryInstitute of Biophysics, Biological Research Centre, Eötvös Loránd Research Network, H-6726 Szeged, HungaryInstitute of Biophysics, Biological Research Centre, Eötvös Loránd Research Network, H-6726 Szeged, HungaryInstitute of Biophysics, Biological Research Centre, Eötvös Loránd Research Network, H-6726 Szeged, HungaryLuxembourg Centre for Systems Biomedicine (LCSB), Developmental and Cellular Biology, University of Luxembourg, 4365 Belvaux, LuxembourgLuxembourg Centre for Systems Biomedicine (LCSB), Developmental and Cellular Biology, University of Luxembourg, 4365 Belvaux, LuxembourgDepartment of Chemical Engineering, National Cheng Kung University, Tainan 70101, TaiwanInstitute of Biophysics, Biological Research Centre, Eötvös Loránd Research Network, H-6726 Szeged, HungaryInstitute of Biophysics, Biological Research Centre, Eötvös Loránd Research Network, H-6726 Szeged, HungaryNanoparticles (NPs) are the focus of research efforts that aim to develop successful drug delivery systems for the brain. Polypeptide nanocarriers are versatile platforms and combine high functionality with good biocompatibility and biodegradability. The key to the efficient brain delivery of NPs is the specific targeting of cerebral endothelial cells that form the blood–brain barrier (BBB). We have previously discovered that the combination of two different ligands of BBB nutrient transporters, alanine and glutathione, increases the permeability of vesicular NPs across the BBB. Our aim here was to investigate whether the combination of these molecules can also promote the efficient transfer of 3-armed poly(<span style="font-variant: small-caps;">l</span>-glutamic acid) NPs across a human endothelial cell and brain pericyte BBB co-culture model. Alanine and glutathione dual-targeted polypeptide NPs showed good cytocompatibility and elevated cellular uptake in a time-dependent and active manner. Targeted NPs had a higher permeability across the BBB model and could subsequently enter midbrain-like organoids derived from healthy and Parkinson’s disease patient-specific stem cells. These results indicate that poly(<span style="font-variant: small-caps;">l</span>-glutamic acid) NPs can be used as nanocarriers for nervous system application and that the right combination of molecules that target cerebral endothelial cells, in this case alanine and glutathione, can facilitate drug delivery to the brain.https://www.mdpi.com/2073-4409/12/3/503brain endothelial cellsblood–brain barrierbrain organoidpeptide nanocarriers3-armed polypeptidesalanine |
| spellingShingle | Mária Mészáros Thi Ha My Phan Judit P. Vigh Gergő Porkoláb Anna Kocsis Emese K. Páli Tamás F. Polgár Fruzsina R. Walter Silvia Bolognin Jens C. Schwamborn Jeng-Shiung Jan Mária A. Deli Szilvia Veszelka Targeting Human Endothelial Cells with Glutathione and Alanine Increases the Crossing of a Polypeptide Nanocarrier through a Blood–Brain Barrier Model and Entry to Human Brain Organoids Cells brain endothelial cells blood–brain barrier brain organoid peptide nanocarriers 3-armed polypeptides alanine |
| title | Targeting Human Endothelial Cells with Glutathione and Alanine Increases the Crossing of a Polypeptide Nanocarrier through a Blood–Brain Barrier Model and Entry to Human Brain Organoids |
| title_full | Targeting Human Endothelial Cells with Glutathione and Alanine Increases the Crossing of a Polypeptide Nanocarrier through a Blood–Brain Barrier Model and Entry to Human Brain Organoids |
| title_fullStr | Targeting Human Endothelial Cells with Glutathione and Alanine Increases the Crossing of a Polypeptide Nanocarrier through a Blood–Brain Barrier Model and Entry to Human Brain Organoids |
| title_full_unstemmed | Targeting Human Endothelial Cells with Glutathione and Alanine Increases the Crossing of a Polypeptide Nanocarrier through a Blood–Brain Barrier Model and Entry to Human Brain Organoids |
| title_short | Targeting Human Endothelial Cells with Glutathione and Alanine Increases the Crossing of a Polypeptide Nanocarrier through a Blood–Brain Barrier Model and Entry to Human Brain Organoids |
| title_sort | targeting human endothelial cells with glutathione and alanine increases the crossing of a polypeptide nanocarrier through a blood brain barrier model and entry to human brain organoids |
| topic | brain endothelial cells blood–brain barrier brain organoid peptide nanocarriers 3-armed polypeptides alanine |
| url | https://www.mdpi.com/2073-4409/12/3/503 |
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