Novel pH-responsive alginate-stabilized curcumin–selenium–ZIF-8 nanocomposites for synergistic breast cancer therapy

Abstract

In this study, a novel selenium@zeolitic imidazolate framework core/shell nanocomposite stabilised with alginate was used to improve the anti-tumour activity of curcumin. The developed alginate-stabilised curcumin-loaded selenium@zeolitic imidazolate framework (Alg@Cur@Se@ZIF-8) had a mean diameter of 159.6 nm and polydispersity index < 0.25. The release of curcumin from the nanocarrier at pH 5.4 was 2.69 folds as high as at pH 7.4. The bare nanoparticles showed haemolytic activity of about 12.16% at a concentration of 500 µg/mL while covering their surface with alginate reduced this value to 5.2%. By investigating cell viability, it was found that Alg@Cur@Se@ZIF-8 caused more cell death than pure curcumin. Additionally, in vivo studies showed that Alg@Cur@Se@ZIF-8 dramatically reduced tumour growth compared to free curcumin in 4T1 tumour-bearing mice. More importantly, the histological study confirmed that the developed drug delivery system successfully inhibited lung and liver metastasis while causing negligible toxicity in vital organs. Overall, due to the excellent inhibitory activity on cancerous cell lines and tumour-bearing animals, Alg@Cur@Se@ZIF-8 can be considered promising for breast cancer therapy.

Keywords:

• Curcumin
• selenium nanocomposite
• ZIF-8
• breast cancer therapy
• pH-responsive

Acknowledgments

The authors would like to acknowledge financial support from the Pharmaceutical Nanotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran (Grant no: A-12-1381-4 (Ethical Code: IR.ZUMS.REC.1399.279) and A-12-1381-25 (Ethical Code: IR.ZUMS.AEC.1402.029)).

Authors’ contributions

The authors confirm their contribution to the paper as follows: study conception and design: Z.K; data collection: E.F., A.A., N.S.; analysis and interpretation of results: Z.K., K.R.; draft manuscript preparation: E.F., Z.K., M.S. All authors reviewed the results and approved the final version of the manuscript.

Disclosure statement

The authors declare that they have no conflicts of interest to disclose.

Data availability statement

The data used to support the findings of this study are available from the corresponding author upon request.