Lapatinib-incorporated lipoprotein-like nanoparticles: Preparation and a proposed breast cancer-targeting mechanism

Li Zhang, Shuang Zhang, Shao Bo Ruan, Qian Yu Zhang, Qin He, Hui Le Gao*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

Abstract

Aim:Lapatinib is a dual inhibitor of EGFR and human epidermal growth factor receptor 2 (HER2), and used to treat advanced breast cancer. To overcome its poor water solubility, we constructed lapatinib-incorporated lipoprotein-like nanoparticles (LTNPs), and evaluated the particle characteristics and possible anti-breast cancer mechanisms.Methods:LTNPs (lapatinib bound to albumin as a core, and egg yolk lecithin forming a lipid corona) were prepared. The particle characteristics were investigated using transmission electron microscopy (TEM) and atomic force microscopy (AFM). The uptake and subcellular localization of LTNPs, as well as the effects of LTNPs on cell cycle were examined in BT-474 human breast cancer cells in vitro. Mice bearing BT-474 subcutaneous xenograft were intravenously injected with coumarin-6 loaded LTNPs (30 mg/kg) to study the targeting mechanisms in vivo.Results:The LTNPs particles were generally spherical but flexible under TEM and AFM, and approximately 62.1 nm in size with a zeta potential of 22.80 mV. In BT-474 cells, uptake of LTNPs was mediated by endosomes through energy-dependent endocytosis involving clathrin-dependent pinocytosis and macropinocytosis, and they could effectively escape from endosomes to the cytoplasm. Treatment of BT-474 cells with LTNPs (20 μg/mL) induced a significant cell arrest at G 0 /G 1 phase compared with the same concentration of lapatinib suspension. In mice bearing BT-474 xenograft, intravenously injected LTNPs was found to target and accumulate in tumors, and colocalized with HER2 and SPRAC (secreted protein, acidic and rich in cysteine).Conclusion:LTNPs can be taken up into breast cancer cells through specific pathways in vitro, and targeted to breast cancer xenograft in vivo via enhanced permeability and retention effect and SPARC.

Original languageEnglish
Pages (from-to)846-852
Number of pages7
JournalActa Pharmacologica Sinica
Volume35
Issue number6
DOIs
Publication statusPublished - Jun 2014
Externally publishedYes

Keywords

  • EGFR
  • HER2
  • Lapatinib
  • breast cancer
  • cell arrest
  • drug delivery
  • drug targeting
  • endosome
  • nanoparticle

Fingerprint

Dive into the research topics of 'Lapatinib-incorporated lipoprotein-like nanoparticles: Preparation and a proposed breast cancer-targeting mechanism'. Together they form a unique fingerprint.

Cite this