The Two Sweet Sides of Janus Lectin Drive Crosslinking of Liposomes to Cancer Cells and Material Uptake
A chimeric, bispecific Janus lectin has recently been engineered with different, rationally oriented recognition sites. It can bind simultaneously to sialylated and fucosylated glycoconjugates. Because of its multivalent architecture, this lectin reaches nanomolar avidities for sialic acid and fucos...
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MDPI AG
2021-11-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/13/11/792 |
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| author | Lina Siukstaite Francesca Rosato Anna Mitrovic Peter Fritz Müller Katharina Kraus Simona Notova Anne Imberty Winfried Römer |
| author_facet | Lina Siukstaite Francesca Rosato Anna Mitrovic Peter Fritz Müller Katharina Kraus Simona Notova Anne Imberty Winfried Römer |
| author_sort | Lina Siukstaite |
| collection | DOAJ |
| description | A chimeric, bispecific Janus lectin has recently been engineered with different, rationally oriented recognition sites. It can bind simultaneously to sialylated and fucosylated glycoconjugates. Because of its multivalent architecture, this lectin reaches nanomolar avidities for sialic acid and fucose. The lectin was designed to detect hypersialylation—a dysregulation in physiological glycosylation patterns, which promotes the tumor growth and progression of several cancer types. In this study, the characteristic properties of this bispecific Janus lectin were investigated on human cells by flow cytometry and confocal microscopy in order to understand the fundamentals of its interactions. We evaluated its potential in targeted drug delivery, precisely leading to the cellular uptake of liposomal content in human epithelial cancer cells. We successfully demonstrated that Janus lectin mediates crosslinking of glyco-decorated giant unilamellar vesicles (GUVs) and H1299 lung epithelial cells. Strikingly, the Janus lectin induced the internalization of liposomal lipids and also of complete GUVs. Our findings serve as a solid proof of concept for lectin-mediated targeted drug delivery using glyco-decorated liposomes as possible drug carriers to cells of interest. The use of Janus lectin for tumor recognition certainly broadens the possibilities for engineering diverse tailor-made lectin constructs, specifically targeting extracellular structures of high significance in pathological conditions. |
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| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-03-10T05:00:34Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
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| series | Toxins |
| spelling | doaj.art-cf9540face79486296349148cedfb5342023-11-23T01:49:11ZengMDPI AGToxins2072-66512021-11-01131179210.3390/toxins13110792The Two Sweet Sides of Janus Lectin Drive Crosslinking of Liposomes to Cancer Cells and Material UptakeLina Siukstaite0Francesca Rosato1Anna Mitrovic2Peter Fritz Müller3Katharina Kraus4Simona Notova5Anne Imberty6Winfried Römer7Faculty of Biology, University of Freiburg, 79104 Freiburg, GermanyFaculty of Biology, University of Freiburg, 79104 Freiburg, GermanyFaculty of Biology, University of Freiburg, 79104 Freiburg, GermanyFaculty of Biology, University of Freiburg, 79104 Freiburg, GermanyFaculty of Biology, University of Freiburg, 79104 Freiburg, GermanyCERMAV, CNRS, University of Grenoble Alpes, CNRS, CERMAV, 38000 Grenoble, FranceCERMAV, CNRS, University of Grenoble Alpes, CNRS, CERMAV, 38000 Grenoble, FranceFaculty of Biology, University of Freiburg, 79104 Freiburg, GermanyA chimeric, bispecific Janus lectin has recently been engineered with different, rationally oriented recognition sites. It can bind simultaneously to sialylated and fucosylated glycoconjugates. Because of its multivalent architecture, this lectin reaches nanomolar avidities for sialic acid and fucose. The lectin was designed to detect hypersialylation—a dysregulation in physiological glycosylation patterns, which promotes the tumor growth and progression of several cancer types. In this study, the characteristic properties of this bispecific Janus lectin were investigated on human cells by flow cytometry and confocal microscopy in order to understand the fundamentals of its interactions. We evaluated its potential in targeted drug delivery, precisely leading to the cellular uptake of liposomal content in human epithelial cancer cells. We successfully demonstrated that Janus lectin mediates crosslinking of glyco-decorated giant unilamellar vesicles (GUVs) and H1299 lung epithelial cells. Strikingly, the Janus lectin induced the internalization of liposomal lipids and also of complete GUVs. Our findings serve as a solid proof of concept for lectin-mediated targeted drug delivery using glyco-decorated liposomes as possible drug carriers to cells of interest. The use of Janus lectin for tumor recognition certainly broadens the possibilities for engineering diverse tailor-made lectin constructs, specifically targeting extracellular structures of high significance in pathological conditions.https://www.mdpi.com/2072-6651/13/11/792chimeric carbohydrateprotein engineeringhypersialylationgiant unilamellar vesiclesdrug deliverycancer cell targeting |
| spellingShingle | Lina Siukstaite Francesca Rosato Anna Mitrovic Peter Fritz Müller Katharina Kraus Simona Notova Anne Imberty Winfried Römer The Two Sweet Sides of Janus Lectin Drive Crosslinking of Liposomes to Cancer Cells and Material Uptake Toxins chimeric carbohydrate protein engineering hypersialylation giant unilamellar vesicles drug delivery cancer cell targeting |
| title | The Two Sweet Sides of Janus Lectin Drive Crosslinking of Liposomes to Cancer Cells and Material Uptake |
| title_full | The Two Sweet Sides of Janus Lectin Drive Crosslinking of Liposomes to Cancer Cells and Material Uptake |
| title_fullStr | The Two Sweet Sides of Janus Lectin Drive Crosslinking of Liposomes to Cancer Cells and Material Uptake |
| title_full_unstemmed | The Two Sweet Sides of Janus Lectin Drive Crosslinking of Liposomes to Cancer Cells and Material Uptake |
| title_short | The Two Sweet Sides of Janus Lectin Drive Crosslinking of Liposomes to Cancer Cells and Material Uptake |
| title_sort | two sweet sides of janus lectin drive crosslinking of liposomes to cancer cells and material uptake |
| topic | chimeric carbohydrate protein engineering hypersialylation giant unilamellar vesicles drug delivery cancer cell targeting |
| url | https://www.mdpi.com/2072-6651/13/11/792 |
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