4.7 Article

Aggressiveness of 4T1 breast cancer cells hampered by Wnt production-2 inhibitor nanoparticles: An in vitro study

Journal

INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 596, Issue -, Pages -

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ELSEVIER
DOI: 10.1016/j.ijpharm.2021.120208

Keywords

Nanoparticles; Peptides; Wnt signaling; Breast cancer

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Polymeric nanoparticles can deliver drugs with lower systemic toxicity to solid tumors, and a new strategy using nanoparticles loaded with Wnt inhibitor IWP-2 significantly reduces tumorigenic capacities in aggressive breast cancer cells through improved solubility and efficacy of the drug.
Polymeric nanoparticles may enable delivery of drugs with lower systemic toxicity to solid tumors. Wnt signaling are evolutionary conserved pathways, involved in proliferation and fate decisions. Alterations in Wnt signaling play a pivotal role in various cancer types that promote cancer initiation, growth, metastasis and drug resistance. We designed a new strategy to allow an efficient targeting of both the canonical and the non-canonical Wnt pathways using nanoparticles loaded with inhibitor of Wnt productions-2 (IWP-2). This hydrophobic drug was successfully co-assembled into NPs composed of poly gamma-glutamic acid and a cationic and amphiphilic b-sheet peptide. Aggressive 4T1 breast cancer cells that were treated with IWP-2 loaded NPs gained a significant decrease in tumorigenic capacities attributed to improved IWP solubility, cellular uptake and efficacy.

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