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

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...

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Bibliographic Details
Published in:International journal of nanomedicine 2012-01, Vol.7 (default), p.3475-3485
Main Authors: Ranjan, Sanjeev, Sood, Rohit, Dudas, Jozsef, Glueckert, Rudolf, Schrott-Fischer, Anneliese, Roy, Soumen, Pyykkö, Ilmari, Kinnunen, Paavo K J
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Cell Line, Tumor
Fluorescent Dyes - chemistry
Fluorescent Dyes - metabolism
Fluorescent Dyes - pharmacokinetics
Histocytochemistry
Humans
Kinetics
liposomes
Liposomes - chemistry
Liposomes - metabolism
Liposomes - pharmacokinetics
Mice
Molecular Sequence Data
Neuroblastoma
Original Research
peptide
Peptides
Peptides - chemistry
Peptides - metabolism
Peptides - pharmacokinetics
Protein Binding
Receptor, trkB - chemistry
Receptor, trkB - metabolism
targeting
tyrosine kinase B
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Summary: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. Binding and internalization of PCL was monitored by flow cytometry and confocal fluorescence microscopy. 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. 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.
ISSN:1178-2013
1176-9114
1178-2013
DOI:10.2147/IJN.S32367