Synthesis and characterization of lipid immuno-nanocapsules for directed drug delivery: selective antitumor activity against HER2 positive breast-cancer cells

Biomacromolecules. 2013 Dec 9;14(12):4248-59. doi: 10.1021/bm401103t. Epub 2013 Nov 4.

Abstract

Lipid nanocapsules (LNC) are usually developed as nanocarriers for lipophilic drug delivery. The surface characteristics of these colloidal particles are determinant for a controlled and directed delivery to target tissues with specific markers. We report the development of immuno-nanocapsules, in which some antibody molecules with different immuno-specificity are conjugated to the nanocapsule surface, offering the standardization of a simple method to obtain vectorized nanosystems with specific recognition properties. Nanocapsules were prepared by a solvent-displacement technique, producing an oily core coated by a functional shell of different biocompatible molecules and surface carboxylic groups. Three different antibodies (one a specific HER2 oncoprotein antibody) were conjugated with these nanoparticles by the carbodiimide method, which allows the covalent immobilization of protein molecules through carboxylic surface groups. The immuno-nanocapsules were completely characterized physico-chemically via electrokinetic and colloidal stability experiments, confirming the correct immobilization of these antibody molecules on the colloidal nanoparticles. Also, additional immunological analyses verified that these IgG-LNC complexes showed the expected specific immuno-response. Finally, different healthy and tumoral breast-cell lines were cultured in vitro with Nile-Red-loaded and docetaxel-loaded HER2 immuno-nanocapsules. The results indicate that our immuno-nanocapsules can increase their uptake in HER2 overexpressing tumoral cell lines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Humanized / chemistry*
  • Antibodies, Monoclonal, Humanized / metabolism
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology
  • Breast Neoplasms
  • Colloids
  • Deoxycholic Acid / chemistry
  • Docetaxel
  • Drug Screening Assays, Antitumor
  • Female
  • Humans
  • Inhibitory Concentration 50
  • MCF-7 Cells
  • Nanocapsules / chemistry*
  • Olive Oil
  • Particle Size
  • Plant Oils / chemistry*
  • Poloxamer / chemistry
  • Receptor, ErbB-2 / metabolism*
  • Taxoids / chemistry*
  • Taxoids / metabolism
  • Taxoids / pharmacology
  • Trastuzumab

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Colloids
  • Nanocapsules
  • Olive Oil
  • Plant Oils
  • Taxoids
  • Deoxycholic Acid
  • Poloxamer
  • Docetaxel
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Trastuzumab