Polyanhydride Copolymer-Based Niclosamide Nanoparticles for Inhibiting Triple-Negative Breast Cancer: Metabolic Responses and Synergism with Paclitaxel

• DOI: 10.1021/acsami.4c17961
• Publication Date: 2024-12-12T22:10:34Z
• Authors: Susheel Kumar Nethi; Siddhant Kothadiya; Brianna M. White; Satyanarayana Rac...; Rizia Bardhan; Surya K. Mallapra...
• Keywords: Niclosamide; Triple-negative breast cancer

The heterogeneity of tumors and the lack effective therapies have resulted in triple-negative breast cancer (TNBC) exhibiting least favorable outcomes among subtypes. TNBC is characterized by its aggressive nature, often leading to high rates relapse, metastasis, mortality. Niclosamide (Nic), an Food Drug Administration-approved anthelmintic drug, has been repurposed for treatment; however, application hindered significant challenges, including strong hydrophobicity, poor aqueous solubility, low bioavailability. This study aimed develop Nic nanoparticles (Nic NPs) using biodegradable biocompatible polyanhydride copolymers enhance Nic's bioavailability therapeutic efficacy. NPs effectively inhibited migration, proliferation, clonogenicity both murine human cells, inducing apoptosis suppressing STAT3 signaling. For first time, we utilized Raman spectroscopy Seahorse extracellular flux assays demonstrate metabolic responses cells NPs, revealing alterations, inhibition mitochondrial respiration glycolysis. Additionally, this explore combination therapy with approved chemotherapeutic agent paclitaxel 4T1 immunocompetent mouse model. significantly reduced tumor growth without adversely affecting body weight tumor-bearing mice. In summary, these findings suggest that could serve as a promising component treatment TNBC.