Targetability of hyaluronic acid nanogel to cancer cells: In vitro and in vivo studies

Eur J Pharm Sci. 2017 Jun 15:104:102-113. doi: 10.1016/j.ejps.2017.03.045. Epub 2017 Apr 4.

Abstract

We have, in previous work developed, characterized and evaluated the biocompatibility of an engineered hyaluronic acid nanogel. Here we assess the targetability of a hyaluronic acid nanogel towards CD44 overexpressing cells, in vitro and in vivo. Results obtained by flow cytometry and confocal fluorescence microscopy shows that nanogel is greatly internalized by non-small cancer lung cells (A549 cells), that overexpress CD44 receptors. The biodistribution and tumor targetability of the nanogel labelled with a near-infrared (NIR) probe were performed, in mice, through a non-invasive imaging system. Results revealed nanogel high targetability towards an induced subcutaneous A549 tumor. Nanogels pharmacokinetics was evaluated also in healthy animals, and Alexa Fluor 680 labelled nanogel exhibited higher accumulation in liver, kidneys and skin. Also, a comparative biodistribution study was performed, using two NIR imaging probes, Cy5.5 and Alexa Fluor 680.

Keywords: Cancer nanotechnology; Hyaluronic acid; Non-invasive imaging; Non-small cancer lung cells.

MeSH terms

  • A549 Cells
  • Animals
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Gels*
  • Humans
  • Hyaluronic Acid / administration & dosage*
  • Hyaluronic Acid / pharmacokinetics
  • In Vitro Techniques
  • Kidney / metabolism
  • Liver / metabolism
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Male
  • Mice, Nude
  • Nanotechnology*
  • Skin / metabolism
  • Spectroscopy, Near-Infrared
  • Tissue Distribution

Substances

  • Gels
  • Hyaluronic Acid