CD44-Targeted Carriers: The Role of Molecular Weight of Hyaluronic Acid in the Uptake of Hyaluronic Acid-Based Nanoparticles
Nanotechnology offers advanced biomedical tools for diagnosis and drug delivery, stressing the value of investigating the mechanisms by which nanocarriers interact with the biological environment. Herein, the cellular response to CD44-targeted nanoparticles (NPs) was investigated. CD44, the main hya...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-01-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/15/1/103 |
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| author | Enrica Chiesa Antonietta Greco Federica Riva Rossella Dorati Bice Conti Tiziana Modena Ida Genta |
| author_facet | Enrica Chiesa Antonietta Greco Federica Riva Rossella Dorati Bice Conti Tiziana Modena Ida Genta |
| author_sort | Enrica Chiesa |
| collection | DOAJ |
| description | Nanotechnology offers advanced biomedical tools for diagnosis and drug delivery, stressing the value of investigating the mechanisms by which nanocarriers interact with the biological environment. Herein, the cellular response to CD44-targeted nanoparticles (NPs) was investigated. CD44, the main hyaluronic acid (HA) receptor, is widely exploited as a target for therapeutic purposes. HA NPs were produced by microfluidic platform starting from HA with different molecular weights (Mw, 280, 540, 820 kDa) by polyelectrolyte complexation with chitosan (CS). Thanks to microfluidic technology, HA/CS NPs with the same physical features were produced, and only the effects of HA Mw on CD44-overexpressing cells (human mesenchymal stem cells, hMSCs) were studied. This work provides evidence of the HA/CS NPs biocompatibility regardless the HA Mw and reveals the effect of low Mw HA in improving the cell proliferation. Special attention was paid to the endocytic mechanisms used by HA/CS NPs to enter hMSCs. The results show the notable role of CD44 and the pronounced effect of HA Mw in the NPs’ internalization. HA/CS NPs uptake occurs via different endocytic pathways simultaneously, and most notably, NPs with 280 kDa HA were internalized by clathrin-mediated endocytosis. Instead, NPs with 820 kDa HA revealed a greater contribution of caveolae and cytoskeleton components. |
| first_indexed | 2024-03-10T00:44:31Z |
| format | Article |
| id | doaj.art-cfe517fb2978483c86d47f9e25cd8033 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T00:44:31Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-cfe517fb2978483c86d47f9e25cd80332023-11-23T15:02:08ZengMDPI AGPharmaceuticals1424-82472022-01-0115110310.3390/ph15010103CD44-Targeted Carriers: The Role of Molecular Weight of Hyaluronic Acid in the Uptake of Hyaluronic Acid-Based NanoparticlesEnrica Chiesa0Antonietta Greco1Federica Riva2Rossella Dorati3Bice Conti4Tiziana Modena5Ida Genta6Department of Surgery, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, ItalyDepartment of Drug Sciences, University of Pavia, 27100 Pavia, ItalyDepartment of Public Health, Experimental and Forensic Medicine, Histology and Embryology Unit, University of Pavia, 27100 Pavia, ItalyDepartment of Drug Sciences, University of Pavia, 27100 Pavia, ItalyDepartment of Drug Sciences, University of Pavia, 27100 Pavia, ItalyDepartment of Drug Sciences, University of Pavia, 27100 Pavia, ItalyDepartment of Drug Sciences, University of Pavia, 27100 Pavia, ItalyNanotechnology offers advanced biomedical tools for diagnosis and drug delivery, stressing the value of investigating the mechanisms by which nanocarriers interact with the biological environment. Herein, the cellular response to CD44-targeted nanoparticles (NPs) was investigated. CD44, the main hyaluronic acid (HA) receptor, is widely exploited as a target for therapeutic purposes. HA NPs were produced by microfluidic platform starting from HA with different molecular weights (Mw, 280, 540, 820 kDa) by polyelectrolyte complexation with chitosan (CS). Thanks to microfluidic technology, HA/CS NPs with the same physical features were produced, and only the effects of HA Mw on CD44-overexpressing cells (human mesenchymal stem cells, hMSCs) were studied. This work provides evidence of the HA/CS NPs biocompatibility regardless the HA Mw and reveals the effect of low Mw HA in improving the cell proliferation. Special attention was paid to the endocytic mechanisms used by HA/CS NPs to enter hMSCs. The results show the notable role of CD44 and the pronounced effect of HA Mw in the NPs’ internalization. HA/CS NPs uptake occurs via different endocytic pathways simultaneously, and most notably, NPs with 280 kDa HA were internalized by clathrin-mediated endocytosis. Instead, NPs with 820 kDa HA revealed a greater contribution of caveolae and cytoskeleton components.https://www.mdpi.com/1424-8247/15/1/103hyaluronic acidCD44 targetingmicrofluidicnanoparticlesendocytic mechanismtransport inhibitors |
| spellingShingle | Enrica Chiesa Antonietta Greco Federica Riva Rossella Dorati Bice Conti Tiziana Modena Ida Genta CD44-Targeted Carriers: The Role of Molecular Weight of Hyaluronic Acid in the Uptake of Hyaluronic Acid-Based Nanoparticles Pharmaceuticals hyaluronic acid CD44 targeting microfluidic nanoparticles endocytic mechanism transport inhibitors |
| title | CD44-Targeted Carriers: The Role of Molecular Weight of Hyaluronic Acid in the Uptake of Hyaluronic Acid-Based Nanoparticles |
| title_full | CD44-Targeted Carriers: The Role of Molecular Weight of Hyaluronic Acid in the Uptake of Hyaluronic Acid-Based Nanoparticles |
| title_fullStr | CD44-Targeted Carriers: The Role of Molecular Weight of Hyaluronic Acid in the Uptake of Hyaluronic Acid-Based Nanoparticles |
| title_full_unstemmed | CD44-Targeted Carriers: The Role of Molecular Weight of Hyaluronic Acid in the Uptake of Hyaluronic Acid-Based Nanoparticles |
| title_short | CD44-Targeted Carriers: The Role of Molecular Weight of Hyaluronic Acid in the Uptake of Hyaluronic Acid-Based Nanoparticles |
| title_sort | cd44 targeted carriers the role of molecular weight of hyaluronic acid in the uptake of hyaluronic acid based nanoparticles |
| topic | hyaluronic acid CD44 targeting microfluidic nanoparticles endocytic mechanism transport inhibitors |
| url | https://www.mdpi.com/1424-8247/15/1/103 |
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