Co-delivery of curcumin and Bcl-2 siRNA to enhance therapeutic effect against breast cancer cells using PEI-functionalized PLGA nanoparticles

Abstract

Purpose

Breast cancer is the second major cause of death worldwide among women. Co-delivery of anticancer drugs and nucleic acids targeting the apoptosis pathway could be a promising new approach.

Methods

In the present study, we synthesized a novel nanostructure for the co-delivery of curcumin and siRNA to breast cancer cells. Curcumin-loaded polylactic-co-glycolic acid (PLGA) was synthesized using an O/W emulsion-solvent diffusion method. It was coated with polyethylenimine (PEI) and subsequently complexed with Bcl-2 siRNA. Also, nanoparticles were characterized such as zeta potential, size distribution and drug encapsulation. Finally, the cytotoxicity of NP and Bcl-2 expression was evaluated.

Results

The curcumin-loaded PLGA nanoparticles were 70 nm in size, and increased to 84 nm after incorporation of PEI plus Bcl-2 siRNA. The encapsulation ratio of the drug in our nanoparticle was 78%. Cellular internalization of PLGA-CUR-PEI/Bcl-2 siRNA NPs was confirmed by fluorescence microscopy with the broadcasting of the fluorescence in the cytoplasm and into the nucleus. The results of the cell viability assay revealed that curcumin-loaded PLGA coated with PEI and Bcl-2 siRNA exhibited the highest cytotoxicity against the T47D cell line, while the siRNA decreased the Bcl-2 expression by 90.7%.

Conclusion

The co-delivery of curcumin plus Bcl-2 siRNA with the PLGA-PEI nanosystem could be a synergistic drug carrier against breast cancer cells.

Graphical Abstract

Keywords:

• Curcumin
• nanodelivery
• Bcl-2 siRNA
• breast cancer
• polylactic-co-glycolic acid

Acknowledgment

Our most special thanks go to Ali Sahebi. We are especially grateful to Yasaman Electriciteh for helping us in this research.

Author contributions

Designed the project: M.K. S.Z Data Collection & Analysis: L.M.G.S., S.Z., E.H., M.B. and F.A. Conducted the experiments: L.M.G.S., E.H., A.H., M.B. and F.A. Wrote the paper: E.H., M.K., S.Z., L.M.G.S, E.H., M.R.H. and M.B All authors read and approved the final manuscript.

Disclosure statement

MRH declares the following potential conflicts of interest. Scientific Advisory Boards: Transdermal Cap Inc, Cleveland, OH; Hologenix Inc. Santa Monica, CA; Vielight, Toronto, Canada; JOOVV Inc, Minneapolis-St. Paul MN; Consulting; USHIO Corp, Japan; Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany. The other authors declare that they have no conflict of interest.

Data availability statement

The data for the present study will be provided upon request.

Additional information

Funding

This study was funded by a grant from the Iran University of Medical Sciences under the grant number: 97-02-117-33563. MRH was supported by US NIH Grants R01AI050875 and R21AI121700.