Kv1.3 Channel inhibition by nanoformulated MeuKTx as a therapeutic strategy in breast cancer.

Breast cancer, particularly invasive and epithelial–mesenchymal transition (EMT)–associated phenotypes, remains a major therapeutic challenge. MeuKTx, a Kv1.3-targeting peptide derived from Mesobuthus eupeus venom, was nanoformulated using chitosan to improve peptide stability and cellular delivery. This study presents the first nano-encapsulation of MeuKTx (NP-MeuKTx) for anticancer evaluation. The resulting nanoparticles exhibited uniform morphology, nanoscale size, and high encapsulation efficiency. NP-MeuKTx exhibited significantly enhanced cytotoxicity compared with free MeuKTx. The IC₅₀ value of free MeuKTx in MCF-7 cells was greater than 400 pM, whereas NP-MeuKTx exhibited a markedly lower IC₅₀ of 25.3 pM. In MCF-7-EMT cells, the IC₅₀ of free MeuKTx was 85.32 pM, which was substantially reduced to 23.27 pM following NP-MeuKTx treatment. Migration assays demonstrated that NP-MeuKTx markedly suppressed cell migration in both MCF-7 and MCF-7-EMT cells, with significantly greater inhibition than free MeuKTx (p ≤ 0.0022). Flow cytometric analysis revealed that NP-MeuKTx induced the highest levels of apoptosis in both cell models, significantly exceeding the effects of free peptide (p = 0.0001). Furthermore, NP-MeuKTx strongly inhibited angiogenesis in HUVEC tube formation assays, significantly reducing branch points, total tube length, and mesh area compared with controls and free MeuKTx (p < 0.0001). Overall, these findings indicate that chitosan-based nanoformulation improves the functional anticancer activity of MeuKTx in breast cancer models.