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Sequence-specific and Selective Recognition of Double-stranded RNAs over Single-stranded RNAs by Chemically Modified Peptide Nucleic Acids

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Dual-targeted polyplexes based on sequence-defined peptide-PEG-oligoamino amides.

Petra Kos¹, Ulrich Lächelt, Dongsheng He

¹Pharmaceutical Biotechnology, Center for System-Based Drug Research, Ludwig-Maximilians-University Munich, Munich, D-81377, Germany.

Journal of Pharmaceutical Sciences

|October 1, 2014

Summary

This study developed dual peptide-targeted polyplexes for cancer cell targeting, mimicking viral strategies. The combination of GE11 and B6 peptides showed the most effective cell binding and gene transfer in prostate cancer cells.

Keywords:

EGFR gene delivery integrin pegylation peptides plasmid DNA polyplex receptors targeting transferrin

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Facile Protocol for the Synthesis of Self-assembling Polyamine-based Peptide Amphiphiles PPAs and Related Biomaterials

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Area of Science:

Biotechnology
Nanomedicine
Cancer Research

Background:

Viruses utilize dual-receptor binding for active cell targeting.
Mimicking this natural process can enhance targeted delivery of therapeutic agents.
Developing efficient cancer cell targeting strategies is crucial for effective treatment.

Purpose of the Study:

To evaluate a dual peptide-based approach for targeting cancer cells.
To design and optimize dual-receptor targeted polyplexes for enhanced delivery.
To investigate the correlation between cell binding and gene transfer efficiency.

Main Methods:

Synthesized sequence-defined oligo(ethane amino)amides with PEGylated peptide ligands.
Utilized peptides targeting integrin (cRGDfk), transferrin receptor (B6), and EGFR (GE11).
Constructed dual-targeted polyplexes and tested them in DU145 prostate cancer cells at different N/P ratios.

Main Results:

Dual targeting effects were most pronounced at a lower nitrogen/phosphate (N/P) ratio of 6.
All three dual-ligand combinations showed enhanced targeting compared to single ligands.
The GE11 plus B6 combination demonstrated the most potent cell binding and pDNA transfection.
GE11 peptide-based polyplexes exhibited bimodal cell association, while others showed monomodal binding.

Conclusions:

Dual peptide-based polyplexes can effectively target cancer cells, mimicking viral strategies.
The combination of GE11 and B6 peptides represents a highly potent strategy for dual-receptor targeting.
A strong correlation exists between cell binding affinity and gene transfer efficiency.
Different ligand combinations can influence cell association profiles, offering tunable targeting characteristics.