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

Pharm Dev Technol. 2022 Sep;27(7):785-793. doi: 10.1080/10837450.2022.2120003. Epub 2022 Sep 7.

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.

Keywords: Bcl-2 siRNA; Curcumin; breast cancer; nanodelivery; polylactic-co-glycolic acid.

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Breast Neoplasms* / drug therapy
  • Cell Line, Tumor
  • Curcumin* / pharmacology
  • Curcumin* / therapeutic use
  • Drug Carriers / chemistry
  • Emulsions
  • Female
  • Glycolates
  • Humans
  • Lactic Acid / chemistry
  • Nanoparticles* / chemistry
  • Polyethyleneimine
  • Polyglycolic Acid / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer / chemistry
  • RNA, Small Interfering / genetics
  • Solvents

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Emulsions
  • Glycolates
  • RNA, Small Interfering
  • Solvents
  • glycolic acid
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Polyethyleneimine
  • Curcumin