Carcinoembryonic antigen-targeted nanoparticles potentiate the delivery of anticancer drugs to colorectal cancer cells

Int J Pharm. 2018 Oct 5;549(1-2):397-403. doi: 10.1016/j.ijpharm.2018.08.016. Epub 2018 Aug 12.

Abstract

Bioengineered functionalized nanoparticles have extensively been proposed in recent years to efficiently deliver anti-cancer drugs to the tumour site, by targeting the cancer cells and improving the therapeutic efficiency of active molecules. In this work, polymeric poly (lactic-co- glycolic)-polyethyleneglycol (PLGA-PEG) nanoparticles were produced by nanoprecipitation and loaded with paclitaxel, following surface-functionalized with a monoclonal antibody targeting the carcinoembryonic antigen (CEA) of intestinal epithelial cells. Physicochemical properties, cytotoxicity and targeting ability of the nanoparticles against two intestine epithelial carcinoma cell lines, CEA-expressing Caco-2 clone and non-CEA-expressing SW480, were assessed. Results showed successful production of nanoparticles around 200 nm, and close to charge neutrality, encapsulating up to 99% of paclitaxel. Functionalized nanoparticles were further constructed, demonstrating to be non-cytotoxic against intestinal cells. The targeting ability of functionalized nanoparticles to Caco-2 CEA expressing cells was confirmed by flow cytometry, in opposite to SW480 cells. Overall, the surface-modified PLGA-PEG nanoparticles with the CEA-targeting antibody were successfully developed as nanocarriers for paclitaxel and interacted with CEA expressing cells. This specific interaction provide these particles ability to be used as targeted systems for colorectal cancer therapeutics.

Keywords: Carcinoembryonic antigen; Colorectal cancer; Drug delivery; Targeted nanoparticles.

Publication types

  • Comparative Study

MeSH terms

  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / metabolism*
  • Carcinoembryonic Antigen / immunology
  • Carcinoembryonic Antigen / metabolism*
  • Cell Survival / drug effects
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / immunology
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Drug Carriers*
  • Drug Compounding
  • Drug Liberation
  • Humans
  • Nanomedicine
  • Nanoparticles*
  • Paclitaxel / chemistry
  • Paclitaxel / metabolism
  • Paclitaxel / pharmacology*
  • Particle Size
  • Polyethylene Glycols / chemistry*
  • Polyglactin 910 / chemistry*
  • Solubility
  • Surface Properties
  • Technology, Pharmaceutical / methods
  • Tubulin Modulators / chemistry
  • Tubulin Modulators / metabolism
  • Tubulin Modulators / pharmacology*

Substances

  • Antibodies, Monoclonal
  • Carcinoembryonic Antigen
  • Drug Carriers
  • Tubulin Modulators
  • poly(lactic-glycolic acid)-poly(ethyleneglycol) copolymer
  • Polyglactin 910
  • Polyethylene Glycols
  • Paclitaxel