Recombinant IκBα-loaded curcumin nanoparticles for improved cancer therapeutics

Nanotechnology. 2014 Aug 29;25(34):345102. doi: 10.1088/0957-4484/25/34/345102. Epub 2014 Aug 5.

Abstract

The field of recombinant protein therapeutics has been evolving rapidly, making significant impact on clinical applications for several diseases, including cancer. However, the functional aspects of proteins rely exclusively on their structural integrity, in which nanoparticle mediated delivery offers unique advantages over free proteins. In the present work, a novel strategy has been developed where the nanoparticles (NPs) used for the delivery of the recombinant protein could contribute to enhancing the therapeutic efficacy of the recombinant protein. The transcription factor, NFκB, involved in cell growth and its inhibitor, IκBα, regulates its proliferation. Another similar naturally available molecule, which inhibits the function of NFκB, is curcumin. Hence, we have developed a 'green synthesis' method for preparing water-soluble curcumin nanoparticles to stabilize recombinant IκBα protein. The NPs were characterized by UV-vis and fluorescence spectroscopy, transmission electron microscopy (TEM) and dynamic light scattering before administration into human cervical carcinoma (HeLa) and glioblastoma (U87MG) cells. Experimental results demonstrated that this combined module had enhanced therapeutic efficacy, causing apoptotic cell death, which was confirmed by cytotoxicity assay and flowcytometry analyses. The expression of apoptotic genes studied by semi-quantitative reverse transcription PCR delineated the molecular pathways involved in cell death. Thus, our study revealed that the functional delivery of recombinant IκBα-loaded curcumin NPs has promise as a natural-product-based protein therapeutics against cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Apoptosis
  • Curcumin / administration & dosage*
  • Curcumin / therapeutic use
  • Drug Delivery Systems
  • HeLa Cells
  • Humans
  • I-kappa B Proteins / administration & dosage*
  • I-kappa B Proteins / genetics
  • I-kappa B Proteins / therapeutic use
  • NF-KappaB Inhibitor alpha
  • Nanoparticles / chemistry
  • Nanoparticles / therapeutic use*
  • Neoplasms / drug therapy*
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / therapeutic use

Substances

  • I-kappa B Proteins
  • NFKBIA protein, human
  • Recombinant Proteins
  • NF-KappaB Inhibitor alpha
  • Curcumin