Wnt signaling inhibition using IWP-2 loaded polypeptide-peptide nanoparticles for decreasing tumor progression

Wnt signaling pathways are evolutionary conserved among metazoan, regulating various cellular activities including proliferation and fate decisions. Alterations in Wnt signaling were found to play a pivotal role in cancer and other diseases. Downstream effectors of the canonical Wnt signaling that were dysregulated by the co-transcriptional factor β-catenin were found to affect cancer initiation. Furthermore, it was recently suggested that a transition between the canonical to the non-canonical Wnt pathways is correlated with acquisition of more tumorigenic properties such metastases and drug resistance. Therefore, a new strategy for an efficient targeting of Wnt pathways was developed in this research. In this strategy we combine specially designed nanoparticles (NPs), 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, with Wnt production inhibitor (IWP-2). We applied this new strategy in models of aggressive metastatic breast cancer. BC cells that were treated with IWP-2-PoP-NPs showed a significant decrease in tumorigenic capacities in comparison with cells that were treated with IWP-2 directly. These results suggest that the NPs improve IWP solubility, promote its cellular uptake,leading to hampered activities of these cancer cells.