Development and Characterization of Curcumin Loaded PEGylated Niosomal Nanoparticles: Potential Anti-Cancer Effect on Breast Cancer Cells through RFC Gene Expression

Asian Pac J Cancer Prev. 2025 Mar 1;26(3):1017-1026. doi: 10.31557/APJCP.2025.26.3.1017.

Abstract

Background: Breast cancer is the second leading cause of cancer deaths among women. Recent studies emphasize the significant role of folate metabolic pathways in cancer progression. The Reduced Folate Carrier (RFC), a folate transporter in cell membranes, plays an essential role in transporting folate receptor-dependent drugs. Curcumin, a bioactive compound with anticancer and anti-inflammatory effects, is hindered by low stability and a short half-life. Niosomes are versatile nanoparticles that can deliver both hydrophilic and hydrophobic drugs.

Objective: This study aims to evaluate the anticancer effects of curcumin-loaded niosomal nanoparticles, focusing on their impact on RFC, BAX, and BCL-2 gene expression in MDA-MB-231 breast cancer cells.

Methods: Curcumin-loaded noisomal nanoparticles were synthesized by the thin-film hydration method. Then, the morphology, size, and physico-chemical nanoparticles were determined by FE-SEM, DLS, and FT-IR methods, respectively. The MTT results determined the cytotoxicity of free and nano-formulated curcumin; also, the gene expression of RFC, BCL-2, and BAX was evaluated using the Real-Time PCR method. Furthermore, apoptosis and cell cycle analysis were investigated by Flow cytometry. Results: The results of the physicochemical characteristics of the nanoparticles showed that curcumin was appropriately loaded in niosomal NPs. The MTT results showed that curcumin loaded in niosomal NPs has a higher anti-proliferative effect than free curcumin. Real-time PCR results showed increased RFC and BAX gene expression and decreased BCL-2 gene expression; this change was more significant in the treatment with nano-formulated curcumin. The apoptosis and cell cycle analysis also confirmed that free and nano-formulated curcumin induces apoptosis and cell cycle arrest. Conclusion: Overall, the results suggested that curcumin loaded in niosomal nanoparticles effectively improves the anticancer effect and could be a capable approach for treating breast cancer.

Keywords: Niosome nanoparticles; Reduced folate carrier; breast cancer; curcumin.

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Apoptosis / drug effects
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / pathology
  • Cell Proliferation / drug effects
  • Curcumin* / chemistry
  • Curcumin* / pharmacology
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Liposomes / chemistry
  • Nanoparticles* / chemistry
  • Polyethylene Glycols* / chemistry
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Reduced Folate Carrier Protein* / genetics
  • Reduced Folate Carrier Protein* / metabolism
  • Tumor Cells, Cultured
  • bcl-2-Associated X Protein / genetics

Substances

  • Curcumin
  • Liposomes
  • Polyethylene Glycols
  • Antineoplastic Agents
  • Reduced Folate Carrier Protein
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein