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Maokai Xu

Investigation of Gb3-binding lectins as drug delivery tools that cross membrane barriers

Principal investigator: Prof. Dr. Winfried Römer

Centre for Biological Signalling Studies (BIOSS)
Schänzlestraße 18
79104 Freiburg

Phone: +49 (0) 76 203 67503
maokai.xu@bioss.uni-freiburg.de
 

 

Abstract

Decades of dedicated efforts have been invested in the field of drug delivery targeting many diseases, such as cancer, diabetes, and neurodegenerative diseases. Biological barriers in human bodies are one big obstacle for therapeutic drugs because the transport efficiency of drugs is highly decreased, specifically through the blood-brain barrier [1]. Among all the strategies of drug delivery, receptor-mediated transport is represented as one of the most efficient ways to transfer the conjugated drugs towards the organs when recognizing the endogenous receptors.

Lipids that form the membranes of transcytosis vesicles have been shown to transcytoses at considerable rates. Especially glycosphingolipids are attractive candidates as receptors for transcytotic drug delivery because they expressed highly in specific disease organs and possess glycostructures as headgroups for which specific ligands exist [2]. Recently, two glycosphingolipid Gb3-binding lectins: Shiga toxin B-subunit (StxB) and the P. aeruginosa lectin LecA were found to undergo the transcytosis over epithelial cell layers in the apical to the basolateral direction and in the opposite direction after binding to Gb3 [3]. However, they showed a different trafficking route after internalization, approximately 50% of StxB reached the Golgi apparatus via retrograde transport, whereas less than 15% of LecA was retrogradely trafficked. Both performed considerate efficiency rate of transcytosis in our former basis research which means they can be used in a potential drug carry.  

In the framework of the doctoral project, I want to study the potential utilization of Gb3-binding lectins in drug delivery, and the mechanism of transport through the membranes and organized trafficking pathways increases the transport of fusion proteins.

Methods

  • Culture of polarized cells
  • Protein conjugation/fusion protein expression and purification
  • Immunofluorescence
  • Confocal microscopy

 

References

  1. Abdul Razzak, R.; Florence, G.J.; Gunn-Moore, F.J. Approaches to CNS Drug Delivery with a Focus on Transporter-Mediated Transcytosis. International journal of molecular sciences 2019, 20.
  2. Thuenauer, R.; Müller, S.K.; Römer, W. Pathways of protein and lipid receptor-mediated transcytosis in drug delivery. Expert Opinion on Drug Delivery 2017, 14, 341–351.
  3. Müller, S.K.; Wilhelm, I.; Schubert, T.; Zittlau, K.; Imberty, A.; Madl, J.; Eierhoff, T.; Thuenauer, R.; Römer, W. Gb3-binding lectins as potential carriers for transcellular drug delivery. Expert Opinion on Drug Delivery 2017, 14, 141–153.