p53 gene therapy of human breast carcinoma: using a transferrin-modified silica nanoparticles

Breast Cancer. 2016 Jan;23(1):101-110. doi: 10.1007/s12282-014-0537-z. Epub 2014 May 4.

Abstract

Background: Nanoparticles have an enormous potential for development in biomedical applications, such as gene or drug delivery. In our study, we examined the efficacy of p53 gene therapy in human breast carcinoma (MCF-7) cells using silica nanoparticles (SiNPs) supplemented with transferrin.

Methods: MCF-7 cells were exposed to transferrin-SiNPs-p53 in vitro, and the growth inhibition rate, expression of p53 and bax, and induction of apoptosis were measured 48 h later.

Results: Treatment of MCF-7 cells with transferrin-SiNPs-p53 resulted in 60.7 % growth inhibition. Wild-type p53 expression and an increase in bax expression were observed following transfection with transferrin-SiNPs-p53, and 20.5 % of the treated MCF-7 cells were apoptotic. In vivo, the MCF-7 tumor transplanted into nude mice grew to 5-6 mm in diameter. Following growth of the tumor to this size, transferrin-SiNPs-p53 was locally applied to the peripheral tumor (day 0) and then applied once every 5 days for a total of six times. During the administration period, tumor growth did not occur, and the mean tumor volume on the last day of administration (day 25) was 10.0 % of that in the saline control group.

Conclusion: These results suggest that p53 gene therapy via transferrin-modified silica nanoparticles is an effective strategy for treatment of breast carcinoma.

Keywords: Breast carcinoma; Gene delivery; Silica nanoparticles; Transferrin (Tf); p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Blotting, Western
  • Breast Neoplasms / genetics
  • Breast Neoplasms / therapy*
  • Carcinoma / genetics
  • Carcinoma / therapy*
  • Cell Proliferation / genetics*
  • Female
  • Genes, p53*
  • Genetic Therapy / methods*
  • Humans
  • In Situ Nick-End Labeling
  • In Vitro Techniques
  • MCF-7 Cells
  • Mice
  • Mice, Nude
  • Nanoparticles*
  • Neoplasm Transplantation
  • Receptors, Transferrin / metabolism
  • Silicon Dioxide*
  • Transfection
  • Transferrin*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • bcl-2-Associated X Protein / metabolism*

Substances

  • Receptors, Transferrin
  • TP53 protein, human
  • Transferrin
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • Silicon Dioxide