Peptide-mediated targeting of liposomes to TrkB receptor-expressing cells
Sanjeev Ranjan1, Rohit Sood, Jozsef Dudas
1Helsinki Biophysics and Biomembrane Group, Department of Biomedical Engineering and Computational Science, Aalto University, Espoo, Finland.
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.
Insights
Targeted liposomes effectively bind and are internalized by TrkB-expressing cells. This peptide-conjugated liposome (PCL) delivery system shows promise for TrkB-targeted therapies in neuroblastoma and other cancers.
Area of Science:
- Cell biology
- Nanomedicine
- Biotechnology
Background:
- The neurotrophic receptor tyrosine kinase B (TrkB) plays critical roles in both neuronal survival and tumor cell signaling, making it a target for neuroblastoma and other cancers.
- TrkB's dual role necessitates targeted delivery strategies for therapeutic intervention, balancing its function in neurons versus tumor cells.
Purpose of the Study:
- To investigate the feasibility of targeting TrkB-expressing cells using peptide-conjugated liposomes (PCL).
- To evaluate the binding and internalization efficiency of TrkB-targeted PCL in relevant cell models.
Main Methods:
- Utilized flow cytometry and confocal fluorescence microscopy to monitor PCL binding and internalization.
- Employed TrkB-expressing mouse macrophage-like RAW264 cells and human neuroblastoma SH-SY5Y cells (treated with all-trans-retinoic acid).
Main Results:
- TrkB-targeted PCL demonstrated enhanced and faster internalization by RAW264 cells compared to scrambled peptide controls.
- Augmented binding and uptake of targeted PCL were observed in TrkB-positive SH-SY5Y cells, with cytoplasmic localization within 20 minutes.
Conclusions:
- Demonstrated the successful targeting of liposomes to TrkB-expressing cells using 18-mer peptides.
- Confirmed that targeted PCL promotes cellular uptake, at least partially into endosomes, via receptor-mediated pathways.
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