Inhibition of Tumor Related Wnt Signaling Using IWP-2 loaded Polypeptide-peptide Nanoparticles

Background: Wnt signaling pathways are evolutionary conserved among metazoan regulating cellular activities such as proliferation and fate decisions. However, alterations in Wnt signaling play a pivotal role in various cancer types. In the canonical Wnt signaling, its downstream effectors are deregulated via the transcriptional factor β-catenin, affecting mainly cancer initiation. It was recently suggested that a transition between the canonical to the non-canonical pathways is correlated with acquisition of more tumorigenic properties such metastases and drug resistance. Therefore, we designed a new strategy to allow an efficient and promoted targeting of both, the canonical and the non-canonical Wnt pathways in cases of aggressive metastatic breast cancer.

Methods: The canonical and non-canonical Wnt production inhibitor (IWP-2) was incorporated into nanoparticles and evaluated for its effects on tumorigenicity of breast cancer (BC) cell cultures. The nanoparticles developed herein are based on a recently reported self-assembled polypeptide-peptide (PoP-NPs) system comprising of the naturally produced, nontoxic polypeptide, poly-γ-glutamic acid (γ-PGA) and a designed amphiphilic and cationic β-sheet peptide.

Results: BC cells that were treated with IWP-PoP-NPs showed a significant decrease in tumorigenic capacities such as proliferation and migration in comparison with cells that were treated with IWP-2 directly.

Conclusions: These results suggest that the NPs improve IWP solubility, promote its cellular uptake, leading to hampered activities of these cancer cells.