Synthesis, characterization, and cellular uptake of magnetic nanocarriers for cancer drug delivery

J Colloid Interface Sci. 2014 Nov 1:433:76-85. doi: 10.1016/j.jcis.2014.07.013. Epub 2014 Jul 24.

Abstract

Hypothesis: The absence of targetability is the primary inadequacy of conventional chemotherapy. Targeted drug delivery systems are conceptualized to overcome this challenge. We have designed a targetable magnetic nanocarrier consisting of a superparamagnetic iron oxide (SPIO) core and biocompatible and biodegradable poly(sebacic anhydride)-block-methyl ether poly(ethylene glycol) (PSA-mPEG) polymer shell. The idea is that this type of carriers should facilitate the targeting of cancer cells.

Experiments: PSA-mPEG was synthesized with poly-condensation and the in vitro degradation rate of the polymer was monitored by gel permeation chromatography (GPC). The magnetic nanocarriers were fabricated devoid of any surfactants and were capable of carrying high payload of hydrophobic dye. The successful encapsulation of SPIO within the polymer shell was confirmed by TEM. The results we obtained from measuring the size of SPIO loaded in polymeric NPs (SPIO-PNP) by dynamic light scattering (DLS) and iron content measurement of these particles by ICP-MS, indicate that SPIO is the most suitable carrier for cancer drug delivery applications.

Findings: Measuring the hydrodynamic radii of SPIO-PNPs by DLS over one month revealed the high stability of these particles at both body and room temperature. We further investigated the cell viability and cellular uptake of SPIO-PNPs in vitro with MDA-MB-231 breast cancer cells. We found that SPIO-PNPs induce negligible toxicity within a concentration range of 1-2μg/ml. The TEM micrographs of thin cross-sectioned MDA-MBA-231 cells showed internalization of SPIO-PNPs within size range of 150-200nm after 24h. This study has provided a foundation for eventually loading these nanoparticles with anti-cancer drugs for targeted cancer therapy using an external magnetic field.

Keywords: Biocompatibility; Cytotoxicity; Drug delivery; Magnetic nanoparticles; Nanocomposites; Nanoprecipitation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anhydrides* / chemistry
  • Anhydrides* / pharmacokinetics
  • Anhydrides* / pharmacology
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacokinetics
  • Antineoplastic Agents* / pharmacology
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Decanoic Acids* / chemistry
  • Decanoic Acids* / pharmacokinetics
  • Decanoic Acids* / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Female
  • Ferric Compounds* / chemistry
  • Ferric Compounds* / pharmacokinetics
  • Ferric Compounds* / pharmacology
  • Fluorescent Dyes / chemistry
  • Fluorescent Dyes / pharmacokinetics
  • Fluorescent Dyes / pharmacology
  • Humans
  • Nanocapsules / chemistry*
  • Polyethylene Glycols* / chemistry
  • Polyethylene Glycols* / pharmacokinetics
  • Polyethylene Glycols* / pharmacology

Substances

  • Anhydrides
  • Antineoplastic Agents
  • Decanoic Acids
  • Ferric Compounds
  • Fluorescent Dyes
  • Nanocapsules
  • Poly (sebacic anhydride)
  • ferric oxide
  • Polyethylene Glycols
  • monomethoxypolyethylene glycol