Enhanced Antitumor and Antimetastatic Activity of pH-Responsive Curcumin-Loaded Chitosan-Selenium Nanocomposites against Breast Cancer

Due to low toxicity and anti-cancer activity, selenium nanoparticles have been studied to treat various cancers. In the present study, curcumin-loaded selenium-chitosan nanocomposites (CUR-Cs-SeNCs) were prepared, and their inhibitory effect on 4T1 cell line and tumor-bearing mice was reported. FTIR, XRD, EDX, AFM, and SEM analysis confirmed the successful preparation of CUR-Cs-SeNCs. The average size, polydispersity index, and zeta potential of CUR-Cs-SeNCs were 167.43 ± 6.52, 0.18 ± 0.05, and 35.62 ± 5.21 mV, respectively. The cumulative released percentage of curcumin from nanocomposites at pH 5.5 was about 1.8 times higher than at pH 7.4. Moreover, CUR-Cs-SeNCs showed a diffusion-controlled release pattern at pH 6.8 and 5.5. The in vitro cytotoxicity study on 4T1 cells revealed that CUR-Cs-SeNCs dramatically reduced cell proliferation rate compared to pure curcumin. Additionally, the in vivo study confirmed that the CUR-Cs-SeNCs were more successful in reducing the tumor volume than net CUR. More importantly, histopathological studies revealed a more substantial inhibitory effect on tumor growth and liver metastasis of CUR-Cs-SeNCs as compared to free curcumin. No significant signs of toxicity were detected in the vital organs of CUR-Cs-SeNCs-receiving animals. Therefore, considering the pH-dependent release, the improved inhibitory effect on turmeric cells, and the outstanding performance in the animal model, the CUR-Cs-SeNCs may be promising in future tumor management.