Breast cancer targeted chemotherapy based on doxorubicin-loaded bombesin peptide modified nanocarriers

Drug Deliv. 2016 Oct;23(8):2697-2702. doi: 10.3109/10717544.2015.1049721. Epub 2015 Jul 23.

Abstract

Context: Breast cancer is the most common cancer in female population. Breast cancer chemotherapy using doxorubicin (DOX) is well illustrated. However, a significant obstacle for successful chemotherapy with DOX is multidrug resistant (MDR) in breast cancer cells. Targeted nanocarriers have emerged as frontier research for the improvement of cancer chemotherapy.

Objective: Bombesin (Bn)-modified, DOX-loaded solid lipid nanoparticles (Bn-DOX/SLNs) were constructed. Doxorubicin-resistant MCF-7/MDR human breast cancer cells and the cancer animal models were applied for the evaluation of the in vitro and in vivo anti-tumor effect of Bn-DOX/SLNs.

Methods: Bn-conjugated lipids were synthesized. DOX was then loaded into Bn-modified SLNs. The physicochemical properties of the Bn-DOX/SLNs were investigated by particle size and zeta potential measurement, drug loading and drug-entrapment efficiency, and in vitro drug release behavior. In vitro cytotoxicity against MCF-7/MDR cells was investigated, and in vivo anti-tumor of SLNs was evaluated in human breast cancer mice models.

Results: Bn-DOX/SLNs showed an excellent in vitro cytotoxicity and in vivo anti-tumor effect both in MCF-7/MDR breast cancer cells and breast cancer animal model.

Conclusion: The results demonstrated that Bn-DOX/SLNs reversed the resistance of doxorubicin, suggesting that chemotherapy using this kind of targeted nanocarriers may benefit human breast MDR cancer therapy.

Keywords: Bombesin modified; breast cancer; doxorubicin; solid lipid nanoparticles; targeted chemotherapy.

MeSH terms

  • Animals
  • Bombesin / chemistry*
  • Breast Neoplasms / drug therapy*
  • Cell Line, Tumor
  • Doxorubicin / administration & dosage*
  • Doxorubicin / chemistry
  • Drug Carriers / chemistry*
  • Drug Resistance, Multiple / drug effects
  • Drug Resistance, Neoplasm / drug effects
  • Female
  • Humans
  • Lipids / chemistry
  • MCF-7 Cells
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles / chemistry*
  • Particle Size
  • Peptides / chemistry*

Substances

  • Drug Carriers
  • Lipids
  • Peptides
  • Doxorubicin
  • Bombesin