The Two Sweet Sides of Janus Lectin Drive Crosslinking of Liposomes to Cancer Cells and Material Uptake.

Lina Siukstaite,Anna Mitrovic,Francesca Rosato,Katharina Kraus,Winfried Römer,Anne Imberty,Simona Notova,Peter Fritz Müller

doi:10.3390/toxins13110792

Lina Siukstaite, Anna Mitrovic + Show 6 more

Open Access

https://doi.org/10.3390/toxins13110792

Copy DOI

Abstract

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.

Highlights

Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany; Signaling Research Centers BIOSS and CIBSS, University of Freiburg, 79104 Freiburg, Germany
We used giant unilamellar vesicles (GUVs) [41]
With two populations of GUVs, functionalized with either GM3 or FSL-A and monitored the evolving interactions over time

Summary

Introduction

Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany; Signaling Research Centers BIOSS and CIBSS, University of Freiburg, 79104 Freiburg, Germany. 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. Janus lectin mediates crosslinking of glyco-decorated giant unilamellar vesicles (GUVs) and H1299 lung epithelial cells. The Janus lectin induced the internalization of liposomal lipids and 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, targeting extracellular structures of high significance in pathological conditions

Objectives

Methods

Results

Discussion

Conclusion