Peptide-mediated targeting of liposomes to TrkB receptor-expressing cells

Abstract

Background

The neurotrophic receptor tyrosine kinase B (TrkB) has diverse signaling roles in neurons and tumor cells. Accordingly, its suppressive targeting is of interest in neuroblastoma and other tumors, whereas its role in improving survival is focused in neurons. Here we describe targeting of TrkB-binding peptide-conjugated liposomes (PCL) to the TrkB-expressing mouse macrophage-like cell line RAW264, and to all-trans-retinoic acid-treated neuron-like TrkB⁺ SH-SY5Y human neuroblastoma cells.

Methods

Binding and internalization of PCL was monitored by flow cytometry and confocal fluorescence microscopy.

Results

Internalization of TrkB-targeted PCL by RAW264 cells was enhanced and faster when compared with PCL having the corresponding scrambled peptide. Likewise, binding and augmented uptake were confirmed for TrkB⁺ SH-SY5Y cells, with targeted PCL appearing in the cytoplasm after 20 minutes of incubation.

Conclusion

We demonstrate here the feasibility of targeting liposomes to TrkB-expressing cells by 18-mer peptides, promoting cellular uptake (at least partly into endosomes) via receptor-mediated pathways.

Keywords:

• liposomes
• targeting
• tyrosine kinase B
• peptide

Acknowledgments

This work was supported by the integrated NANOEAR European Union FP6 project (NMP4-CT-2006-026556). SR was also supported by the Magnus Ehrnrooth Foundation, and RS was supported by the Instrumentarium Foundation. The authors thank past and current members of the NANOEAR consortium who contributed to our discussions on targeting peptides and the assay conditions used in the present study, and the skilled laboratory personnel of the Pyykkö Laboratory for assistance with the cell experiments.

Disclosure

The authors report no conflicts of interest in this work.