Trastuzumab modified silica nanoparticles loaded with doxorubicin for targeted and synergic therapy of breast cancer

Artif Cells Nanomed Biotechnol. 2018;46(sup3):S556-S563. doi: 10.1080/21691401.2018.1501380. Epub 2018 Aug 27.

Abstract

Untargeted delivery as well as low efficacy are two main obstacles for effective breast cancer therapy. Here in this study, we surface modified silica nanoparticles (SLN) with Trastuzumab (Tra) to construct a tumor-targeting carrier (Tra-SLN) for specific drug delivery to human epidermal growth factor receptor 2 (HER2) overexpressing breast cancer cells. In addition, Tra-SLN could also loaded with broad-spectrum anticancer drug doxorubicin (DOX) to finally construct a drug delivery system (DDS) capable of co-delivering Tra and DOX (Tra-SLN/DOX). Our results demonstrated that the as-prepared Tra-SLN/DOX was nanoscale particles with spheroid appearance which showed preferable stability in physiological environments. In addition, the Tra-SLN/DOX could specifically target to HER2 overexpressed MCF-7 cells. Both in vitro and in vivo experiments revealed that the Tra-SLN/DOX exerted enhanced anticancer efficacy when compared with Tra or DOX alone. It was suggested that Tra-SLN/DOX might be a promising platform for enhanced therapy of breast cancer.

Keywords: Trastuzumab; breast cancer; doxorubicin; silica nanoparticles; synergic therapy.

MeSH terms

  • Animals
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Doxorubicin* / chemistry
  • Doxorubicin* / pharmacokinetics
  • Doxorubicin* / pharmacology
  • Drug Delivery Systems / methods*
  • Female
  • Humans
  • MCF-7 Cells
  • Mice
  • Nanoparticles* / chemistry
  • Nanoparticles* / therapeutic use
  • Receptor, ErbB-2 / metabolism
  • Silicon Dioxide* / chemistry
  • Silicon Dioxide* / pharmacokinetics
  • Silicon Dioxide* / pharmacology
  • Trastuzumab* / chemistry
  • Trastuzumab* / pharmacokinetics
  • Trastuzumab* / pharmacology
  • Xenograft Model Antitumor Assays

Substances

  • Silicon Dioxide
  • Doxorubicin
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Trastuzumab