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

Abstract

Sanjeev Ranjan,1 Rohit Sood,1 Jozsef Dudas,2 Rudolf Glueckert,2 Anneliese Schrott-Fischer,2 Soumen Roy,2 Ilmari Pyykkö,3 Paavo KJ Kinnunen11Helsinki Biophysics and Biomembrane Group, Department of Biomedical Engineering and Computational Science, Aalto University, Espoo, Finland; 2Department of Otorhinolaryngology, Innsbruck Medical University, Innsbruck, Austria; 3Department of Otolaryngology, University of Tampere Medical School, Tampere, FinlandBackground: 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